|Publication number||US8173062 B1|
|Application number||US 10/956,911|
|Publication date||May 8, 2012|
|Priority date||Sep 30, 2004|
|Publication number||10956911, 956911, US 8173062 B1, US 8173062B1, US-B1-8173062, US8173062 B1, US8173062B1|
|Inventors||Jonathan P. Durcan|
|Original Assignee||Advanced Cardiovascular Systems, Inc.|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (385), Non-Patent Citations (41), Referenced by (8), Classifications (27), Legal Events (2)|
|External Links: USPTO, USPTO Assignment, Espacenet|
1. Field of the Invention
This invention relates to methods of forming radially expandable medical articles through deformation of a polymeric material.
2. Description of the State of the Art
This invention relates to medical article such as expandable medical devices used in the treatment of diseased portions of bodily lumen. Expandable medical devices may include certain kinds of implantable endoprosthesis and inflatable members. Inflatable members such as balloons are used, for example, in angioplasty procedures or in implantation of endoprosthesis which are adapted to be implanted in a bodily lumen. An “endoprosthesis” corresponds to an artificial device that is placed inside the body. A “lumen” refers to a cavity of a tubular organ such as a blood vessel. A stent is an example of such an endoprosthesis. Stents are generally cylindrically shaped devices which function to hold open and sometimes expand a segment of a blood vessel or other anatomical lumen such as urinary tracts and bile ducts. Stents are often used in the treatment of atherosclerotic stenosis in blood vessels. “Stenosis” refers to a narrowing or constriction of the diameter of a bodily passage or orifice. In such treatments, stents reinforce body vessels and prevent restenosis following angioplasty in the vascular system. “Restenosis” refers to the reoccurrence of stenosis in a blood vessel or heart valve after it has been treated (as by balloon angioplasty or valvuloplasty) with apparent success.
The treatment of a diseased site or lesion with a stent involves both delivery and deployment of the stent. “Delivery” refers to introducing and transporting the stent through a bodily lumen to a region, such as a lesion, in a vessel that requires treatment. “Deployment” corresponds to the expanding of the stent within the lumen at the treatment region. Delivery and deployment of a stent are accomplished by positioning the stent about one end of a catheter, inserting the end of the catheter through the skin into a bodily lumen, advancing the catheter in the bodily lumen to a desired treatment location, expanding the stent at the treatment location, and removing the catheter from the lumen. In the case of a balloon expandable stent, the stent is mounted about a balloon disposed on the catheter. Mounting the stent typically involves compressing or crimping the stent onto the balloon. The stent is then expanded by inflating the balloon. The balloon may then be deflated and the catheter withdrawn. In the case of a self-expanding stent, the stent may be secured to the catheter via a retractable sheath or a sock. When the stent is in a desired bodily location, the sheath may be withdrawn which allows the stent to self-expand.
The stent must be able to satisfy a number of mechanical requirements. First, the stent must be capable of withstanding the structural loads, namely radial compressive forces, imposed on the stent as it supports the walls of a vessel lumen. Therefore, a stent must possess adequate radial strength. Radial strength, which is the ability of a stent to resist radial compressive forces, is due to strength and rigidity along the circumferential direction of the stent. Radial strength and rigidity, therefore, may be also be described as, hoop or circumferential strength and rigidity. Additionally, the stent should also be longitudinally flexible to allow it to be maneuvered through a tortuous vascular path and to enable it to conform to a deployment site that may not be linear or may be subject to flexure. The material from which the stent is constructed must allow the stent to undergo expansion which typically requires substantial deformation of localized portions of the stent's structure. Once expanded, the stent must maintain its size and shape throughout its service life despite the various forces that may come to bear on it, including the cyclic loading induced by the beating heart. Finally, the stent must be biocompatible so as not to trigger any adverse vascular responses.
The structure of a stent is typically composed of scaffolding that includes a pattern or network of interconnecting structural elements or struts. The scaffolding can be formed from wires, tubes, or sheets of material rolled into a cylindrical shape. The scaffolding is designed to allow the stent to be radially expandable. The pattern should be designed to maintain the longitudinal flexibility and radial rigidity required of the stent. Longitudinal flexibility facilitates delivery of the stent and radial rigidity is needed to hold open a bodily lumen.
Stents have been made of many materials such as metals and polymers, including biodegradable polymer materials. A medicated stent may be fabricated by coating the surface of either a metallic or polymeric scaffolding with a polymeric carrier that includes an active agent or drug. In many treatment applications, the presence of a stent in a body may be necessary for a limited period of time until its intended function of, for example, maintaining vascular patency and/or drug delivery is accomplished. Therefore, stents fabricated from biodegradable, bioabsorbable, and/or bioerodable materials such as bioabsorbable polymers may be configured to meet this additional clinical requirement since they may be designed to completely erode after the clinical need for them has ended.
Conventional methods of constructing a stent from a polymer material involve extrusion of a polymer tube based on a single polymer or polymer blend and then laser cutting a pattern into the tube. An advantage of stents fabricated from polymers is that they can possess greater flexibility than metal stents. Other potential shortcomings of metal stents include adverse reactions from the body, nonbioerodability, and non-optimal drug-delivery. However, a disadvantage of polymer stents compared to metal stents, is that polymer stents typically have less circumferential strength and radial rigidity. Inadequate circumferential strength potentially contributes to relatively high recoil of polymer stents after implantation into vessels. Another potential problem with polymer stents is that struts can crack during crimping, especially for brittle polymers. Furthermore, in order to have adequate mechanical strength, polymeric stents may require significantly thicker struts than a metallic stent, which results in an undesirable larger profile. Therefore, methods of manufacturing polymer stents that improve circumferential strength and radial rigidity are desirable. The embodiments presented herein address the issue of improving circumferential strength and radial rigidity in polymer stents.
As indicated above, inflatable members may include angioplasty and stent delivery balloons. Angioplasty and stent delivery balloons are typically made of polymeric materials. In general, the polymeric material is extruded into tubular shapes or parisons. The extruded parison is then formed into the balloon shape using a blow molding process. A balloon blow molding process includes a mold, a temperature source, a pressure source, and a tension source. In the balloon molding process, the extruded tubing is placed inside the mold and subsequently the mold is heated with the temperature source. The tubing may be stretched longitudinally under the influence of the tension source and is expanded under the influence of the pressure source. The pressure source typically consists of a nozzle connected to one end of the parison. The nozzle is configured to blow air into the parison to expand the parison within the confines of the mold. The final balloon shape is primarily determined by the geometric design of the mold and process parameters.
Furthermore, high circumferential strength and modulus are also extremely important for inflatable members, such as catheter balloons for use in angioplasty procedures and for delivering stents. Additionally, thinner walls are also strongly desirable for inflatable members since a low form factor of the balloon facilitates transport of the balloon through a vessel. Methods described above that are typically used for forming inflatable members do not allow adequate control over circumferential strength and modulus, as well as wall thickness. In addition, such methods are unable to fabricate balloons of a desired size out of some materials. Failure of the expanding parison often occurs during fabrication. The shortcomings of inflatable member fabrication are addressed by embodiments presented herein.
The present invention includes embodiments of a method for fabricating a medical article including deforming a polymer tube that is at least partially immersed in a liquid. The immersed tube may be heated with the liquid. An embodiment of the method may further include fabricating an implantable medical device from the deformed tube or using the deformed tube as an inflatable member.
Another aspect of the invention may include deforming a polymer tube at least by increasing a pressure inside of the tube with an incompressible or substantially incompressible fluid. The method may further include fabricating an implantable medical device from the deformed tube or using the deformed tube as an inflatable member.
In a further aspect of the invention a method for fabricating a medical article may include treating at least a portion of a polymeric tube with a solvent capable of inducing crystallization in the polymer. The method may further include deforming the polymer tube. An implantable medical device may then be fabricated from the deformed and treated tube or the deformed and treated tube may be used as an inflatable member.
In addition, a method for fabricating a medical article may include deforming a polymer tube and controlling the deformation of the tube with a movable surface restraining at least a portion of the deforming tube. The method may then include fabricating an implantable medical device from the deformed tube formed with controlled deformation or using the deformed tube formed with controlled deformation as an inflatable member.
Furthermore, an additional aspect of the invention may include deforming a polymer tube within an annular mold member having at least three radially movable restraining members within the annular mold member. The deformation of at least a portion of the tube may be controlled with at least three restraining members configured to restrain the deforming tube. An implantable medical device may then be fabricated from the deformed tube formed with controlled deformation or the deformed tube formed with controlled deformation may be used as an inflatable member.
Another aspect of the invention may include allowing a polymer tube to deform in a first stage within a chamber initially defined by a first restraining surface of an inner mold member slidably disposed at least in part within an outer mold member with a second restraining surface. The method may further include allowing the deformed tube to deform in a second stage within a section of the chamber defined by at least a portion of the second restraining surface after sliding the inner mold member out of the section of the chamber. An implantable medical device may be fabricated from the tube deformed in at least two stages or the tube deformed in at least two stages may be used as an inflatable member.
For the purposes of the present invention, the following terms and definitions apply:
The “glass transition temperature,” Tg, is the temperature at which the amorphous domains of a polymer change from a brittle vitreous state to a solid deformable or ductile state at atmospheric pressure. In other words, the Tg corresponds to the temperature where the onset of segmental motion in the chains of the polymer occurs. When an amorphous or semicrystalline polymer is exposed to an increasing temperature, the coefficient of expansion and the heat capacity of the polymer both increase as the temperature is raised, indicating increased molecular motion. As the temperature is raised the actual molecular volume in the sample remains constant, and so a higher coefficient of expansion points to an increase in free volume associated with the system and therefore increased freedom for the molecules to move. The increasing heat capacity corresponds to an increase in heat dissipation through movement. Tg of a given polymer can be dependent on the heating rate and can be influenced by the thermal history of the polymer. Furthermore, the chemical structure of the polymer heavily influences the glass transition by affecting mobility.
“Stress” refers to force per unit area, as in the force acting through a small area within a plane. Stress can be divided into components, normal and parallel to the plane, called normal stress and shear stress, respectively. Tensile stress, for example, is a normal component of stress applied that leads to expansion (increase in volume and/or length). In addition, compressive stress is a normal component of stress applied to materials resulting in their compaction (decrease in volume and/or length). Stress may result in deformation of a material, which refers to change in length and/or volume. “Expansion” or “compression” may be defined as the increase or decrease in length and/or volume of a sample of material when the sample is subjected to stress. “Strain” refers to the amount of expansion or compression that occurs in a material at a given stress or load. Strain may be expressed as a fraction or percentage of the original length, i.e., the change in length divided by the original length. Strain, therefore, is positive for expansion and negative for compression.
Furthermore, a property of a material that quantifies a degree of deformation with applied stress is the modulus. “Modulus” may be defined as the ratio of a component of stress or force per unit area applied to a material divided by the strain along an axis of applied force that results from the applied force. For example, a material has both a tensile and a compressive modulus.
The tensile stress on a material may be increased until it reaches a “tensile strength” which refers to the maximum tensile stress which a material will withstand prior to fracture. The ultimate tensile strength is calculated from the maximum load applied during a test divided by the original cross-sectional area. Similarly, “compressive strength” is the capacity of a material to withstand axially directed pushing forces. When the limit of compressive strength is reached, a material is crushed.
The term “elastic deformation” refers to deformation of an object in which the applied stress is small enough so that the object moves towards its original dimensions or essentially its original dimensions once the stress is released. However, an elastically deformed polymer material may be inhibited or prevented from returning to an undeformed state if the material is below the Tg of the polymer. Below Tg, energy barriers may inhibit or prevent molecular movement that allows deformation or bulk relaxation. “Elastic limit” refers to the maximum stress that a material will withstand without permanent deformation. The term “plastic deformation” refers to permanent deformation that occurs in a material under stress after elastic limits have been exceeded.
“Solvent” is defined as a substance capable of dissolving or dispersing one or more other substances or capable of at least partially dissolving or dispersing the substance(s) to form a uniformly dispersed mixture at the molecular- or ionic-size level. The solvent should be capable of dissolving at least 0.1 mg of the polymer in 1 ml of the solvent, and more narrowly 0.5 mg in 1 ml at ambient temperature and ambient pressure. The “strength” of a solvent refers to the degree to which a solvent may dissolve a polymer. The stronger a solvent, the more polymer the solvent may dissolve.
Embodiments of methods described herein relate to medical articles including implantable medical devices and inflatable members. The implantable medical devices that relate to the embodiments described herein typically include an underlying scaffolding or substrate. The substrate may have a polymer-based coating that may contain, for example, an active agent or drug for local administration at a diseased site. The active agent can be any substance capable of exerting a therapeutic or prophylactic effect. The underlying substrate that is coated can be polymeric, metallic, ceramic, or any suitable material. Implantable medical device is intended to include self-expandable stents, balloon-expandable stents, stent-grafts, grafts (e.g., aortic grafts), artificial heart valves, cerebrospinal fluid shunts, pacemaker electrodes, and endocardial leads (e.g., FINELINE and ENDOTAK, available from Guidant Corporation, Santa Clara, Calif.). The underlying structure or substrate of the device can be of virtually any design.
Polymers can be biostable, bioabsorbable, biodegradable or bioerodable. Biostable refers to polymers that are not biodegradable. The terms biodegradable, bioabsorbable, and bioerodable are used interchangeably and refer to polymers that are capable of being completely degraded and/or eroded when exposed to bodily fluids such as blood and can be gradually resorbed, absorbed, and/or eliminated by the body. The processes of breaking down and eventual absorption and elimination of the polymer can be caused by, for example, hydrolysis, metabolic processes, bulk or surface erosion, and the like. It is understood that after the process of degradation, erosion, absorption, and/or resorption has been completed, no part of the stent will remain or in the case of coating applications on a biostable scaffolding, no polymer will remain on the device. In some embodiments, very negligible traces or residue may be left behind. For stents made from a biodegradable polymer, the stent is intended to remain in the body for a duration of time until its intended function of, for example, maintaining vascular patency and/or drug delivery is accomplished.
The underlying structure or substrate of an implantable medical device, such as a stent can be completely or at least in part be made from a biodegradable polymer or combination of biodegradable polymers, a biostable polymer or combination of biostable polymers, or a combination of biodegradable and biostable polymers. Additionally, a polymer-based coating for a surface of a device can be a biodegradable polymer or combination of biodegradable polymers, a biostable polymer or combination of biostable polymers, or a combination of biodegradable and biostable polymers.
Representative examples of polymers that may be used to fabricate or coat an implantable medical device include, but are not limited to, poly(N-acetylglucosamine) (Chitin), Chitoson, poly(hydroxyvalerate), poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polyorthoester, polyanhydride, poly(glycolic acid), poly(glycolide), poly(L-lactic acid), poly(L-lactide), poly(D,L-lactic acid), poly(D,L-lactide), poly(caprolactone), poly(trimethylene carbonate), polyester amide, poly(glycolic acid-co-trimethylene carbonate), co-poly(ether-esters) (e.g. PEO/PLA), polyphosphazenes, biomolecules (such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronic acid), polyurethanes, silicones, polyesters, polyolefins, polyisobutylene and ethylene-alphaolefin copolymers, acrylic polymers and copolymers other than polyacrylates, vinyl halide polymers and copolymers (such as polyvinyl chloride), polyvinyl ethers (such as polyvinyl methyl ether), polyvinylidene halides (such as polyvinylidene chloride), polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics (such as polystyrene), polyvinyl esters (such as polyvinyl acetate), acrylonitrile-styrene copolymers, ABS resins, polyamides (such as Nylon 66 and polycaprolactam), polycarbonates, polyoxymethylenes, polyimides, polyethers, polyurethanes, rayon, rayon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, and carboxymethyl cellulose. Another type of polymer based on poly(lactic acid) that can be used includes graft copolymers, and block copolymers, such as AB block-copolymers (“diblock-copolymers”) or ABA block-copolymers (“triblock-copolymers”), or mixtures thereof.
Additional representative examples of polymers that may be especially well suited for use in fabricating or coating an implantable medical device include ethylene vinyl alcohol copolymer (commonly known by the generic name EVOH or by the trade name EVAL), poly(butyl methacrylate), poly(vinylidene fluoride-co-hexafluororpropene) (e.g., SOLEF 21508, available from Solvay Solexis PVDF, Thorofare, N.J.), polyvinylidene fluoride (otherwise known as KYNAR, available from ATOFINA Chemicals, Philadelphia, Pa.), ethylene-vinyl acetate copolymers, and polyethylene glycol.
Inflatable members or balloons may be used in catheters for medical, veterinary or research purposes. For example, inflatable members may be used in catheters for human medical treatment, such as, for example, cardiac catheters used in angioplasty or stent delivery for treatment of heart or arterial disorders. Inflatable members are typically made from polymeric materials.
Representative examples of polymeric materials for use in fabricating inflatable members may include, but are not limited to, polyether-block co-polyamide polymers, such as Pebax® resins available from Atofina Chemicals, Inc. in Philadelphia, Pa. (e.g., Pebax® grades 63D, 70D, 72D); polyamides, such as Nylon available from E.I. du Pont de Nemours and Company of Wilmington, Del. (e.g., Nylon 12); polyurethanes; and PTFE fluoropolymer resin (e.g., Teflon® available from E.I. du Pont de Nemours and Company of Wilmington, Del.).
Implantable medical devices and inflatable members are typically subjected to stress during use, both before and during treatment. “Use” includes, but is not limited to, manufacturing, assembling (e.g., crimping stent on inflatable member), delivery of stent and inflatable member and through a bodily lumen to a treatment site, and deployment of stent at a treatment site. Both a scaffolding and a coating on a scaffolding experience stress that result in strain in the scaffolding and/or coating. For example, during deployment, the scaffolding of a stent can be exposed to stress caused by the radial expansion of the stent body. In addition, the scaffolding and/or coating may be exposed to stress when it is mounted on a catheter from crimping or compression of the stent.
It is well known by those skilled in the art of polymer technology that mechanical properties of a polymer may be modified by processes that alter the molecular structure of the polymer. Polymers in the solid state may be completely amorphous, partially crystalline, or almost completely crystalline. Crystalline regions in a polymer are characterized by alignment of polymer chains along the longitudinal or covalent axis of the polymer chains. An oriented crystalline structure tends to have high strength and high modulus (low elongation with applied stress) along an axis of alignment of polymer chains. Therefore, it may be desirable to incorporate processes that induce alignment of polymer chains along a preferred axis or direction into manufacturing methods of implantable medical devices and inflatable members.
Furthermore, molecular orientation in a polymer may be induced, and hence mechanical properties modified, by applying stress to the polymer. The degree of polymer chain alignment induced with applied stress may depend upon the temperature of the polymer. For example, below the glass transition temperature, Tg, of a polymer, polymer segments may not have sufficient energy to move past one another. In general, polymer chain alignment may not be induced without sufficient segmental mobility.
Above Tg, polymer chain alignment may be readily induced with applied stress since rotation of polymer chains, and hence segmental mobility, is possible. Between Tg and the melting temperature of the polymer, Tm, rotational barriers exist, however, the barriers are not great enough to substantially prevent segmental mobility. As the temperature of a polymer is increase above Tg, the energy barriers to rotation decrease and segmental mobility of polymer chains tend to increase. As a result, as the temperature increases, polymer chain alignment is more easily induced with applied stress.
Moreover, application of stress to a polymer may induce polymer chain alignment, and hence, modify its mechanical properties. In particular, polymer chain alignment is more readily induced between Tg and the melting temperature of the polymer, Tm. Rearrangement of polymer chains may take place when a polymer is stressed in an elastic region and in a plastic region of the polymer material. A polymer stressed beyond its elastic limit to a plastic region generally retains its stressed configuration and corresponding induced polymer chain alignment when stress is removed. The polymer chains may become oriented in the direction of the applied stress which results in an oriented crystalline structure. The stressed polymer material may have a higher tensile strength in the direction of the applied stress.
Furthermore, as indicated above, a plastically deformed material tends to retain its deformed configuration once the deforming stress is removed. Stress applied to the material subsequent to the initial deforming stress tends not to cause further deformation of the material unless the applied stress is greater than the initial stress level that caused the deformation. Therefore, the behavior of a plastically deformed material may be more predictable within a range of stress. The stress range may be less than the initial stress applied that caused the plastic deformation.
Additionally, heating a polymer may facilitate deformation of a polymer under stress, and hence, modification of the mechanical properties of the polymer. A polymer deformed elastically with stress facilitated with heating may retain induced polymer chain alignment by cooling the polymer before relaxing to or towards an unstrained state.
Various embodiments of methods for manufacturing implantable medical devices and inflatable members are described herein. In some embodiments, an implantable medical device or an inflatable member may be fabricated from a polymer conduit or tube. The tube may be cylindrical or substantially cylindrical in shape. For example,
Additionally, manufacturing of an implantable medical device, such as a stent, may include forming a pattern that includes a plurality of interconnecting structural elements or struts on a tube. In some embodiments, forming a pattern on a tube may include laser cutting a pattern on the tube. Representative examples of lasers that may be used include an excimer, carbon dioxide, and YAG. In other embodiments, chemical etching may be used to form a pattern on the elongated tube. It is desirable to use a laser cutting technique which minimizes a size of a heat affected zone. A heat affected zone refers to a region of a target material affected by the heat of the laser. Heat from the laser may tend to melt at least a portion of polymer in the heat affected zone. The molecular orientation induced by applied stress may then be dissipated in the melted portion. The corresponding favorable change in mechanical properties may also be reduced.
In addition, as shown in
Due to stresses imposed on an implantable medical device or inflatable member during use, it is important for a device to have adequate strength both in axial and radial or circumferential directions. Therefore, it may be desirable to fabricate an implantable medical device or inflatable member from a polymer tube with adequate strength in the axial direction, as shown by an arrow 35 in
Additionally, conventional fabrication processes of inflatable members inherently induce circumferential alignment of polymer chains since inflatable members are typically formed from a polymer tube by radially deforming the tube to a larger diameter. Some of the embodiments presented herein allow a higher degree of circumferential alignment of polymer chains and result in better induced mechanical properties than conventional methods. Some embodiments also allow a larger degree of deformation or to larger diameters without failure of the polymer.
Polymer tubes may be formed by means of various types of methods, including, but not limited to extrusion or injection molding. Alternatively, a polymer tube may be formed from sheets or films that are rolled and bonded. In extrusion, a polymer melt is conveyed through an extruder which is then formed into, a tube. Extrusion tends to impart large forces on the molecules in the axial direction of the tube due to shear forces on the polymer melt. The shear forces arise from forcing the polymer melt through a die and pulling and forming the polymer melt into the small dimensions of a tube. As a result, polymer tubes formed by conventional extrusion methods tend to possess a significant degree of axial polymer chain alignment. However, such conventionally extruded tubes tend to possess no or substantially no polymer chain alignment in the circumferential direction.
Since the degree of polymer chain alignment is not the same in the axial and circumferential directions, the mechanical properties may also be different in the two directions. This difference may lead to mechanical instability in a fabricated implantable medical device or inflatable member. To reduce or eliminate this difference and increase the circumferential strength and modulus, a tube may be radially deformed between 20% and 900%, or more narrowly, between 100% and 400%.
Therefore, certain embodiments of manufacturing implantable medical devices or inflatable members may include inducing circumferential polymer chain alignment in a polymer tube through radial deformation to increase the circumferential strength and modulus. Circumferential polymer chain alignment may be induced in a tube after fabrication of a tube by extrusion, for example.
In some embodiments, a polymer tube may be deformed at a temperature below the Tg of the polymer. Alternatively, it may be desirable to deform the tube in a temperature range greater than or equal to the Tg of the polymer and less than or equal to the Tm of the polymer. As indicated above, a polymeric material deforms much more readily due to segmental motion of polymer chains above Tg. Deformation induces polymer chain alignment that may occur due to the segmental motion of the polymer chains. Therefore, heating the polymer tube prior to or contemporaneously with deformation may facilitate deformation particularly for polymers with a Tg below an ambient temperature. Heating the tube contemporaneously with the deformation may be desirable since the deformation may occur at a constant or nearly constant temperature. Therefore, the induced polymer alignment and material properties may be constant or nearly constant.
In some embodiments, a polymer tube for fabrication of an implantable medical device or an inflatable member may be deformed radially by increasing a pressure in a polymer tube, for example, by conveying a fluid into the tube. Tension and/or torque may also be applied to the tube. The tube may be positioned in an annular member or mold. The mold may act to control the degree of radial deformation of the tube by limiting the deformation of the outside diameter or surface of the tube to the inside diameter of the mold. The inside diameter of the mold may correspond to a diameter less than or equal to a desired diameter of the polymer tube.
The polymer tube may also be heated prior to, during, and subsequent to the deformation. In general, it is desirable for the temperature during deformation to be greater than or equal to a glass transition temperature of the polymer and less than or equal to a melting temperature of the polymer. The polymer tube may be heated by the fluid and/or the mold.
Certain embodiments may include first sealing, blocking, or closing a polymer tube at a distal end. The end may be open in subsequent manufacturing steps. A fluid, (conventionally an inert gas such as air, nitrogen, oxygen, argon, etc.) may then be conveyed into a proximal end of the polymer tube to increase the pressure in the tube. The pressure of the fluid in the tube may act to deform the tube.
The increased pressure may deform the tube radially and/or axially. The fluid temperature and pressure may be used to control the degree of radial deformation by limiting deformation of the inside diameter of the tube as an alternative to or in combination with using the mold. In addition, it may be desirable to increase the pressure to less than about an ultimate stress of the polymer to inhibit or prevent damage to the tube. The polymer may be deformed plastically or elastically. As indicated above, a polymer elongated beyond its yield point tends to retain its expanded configuration, and hence, tends to retain the induced molecular orientation.
Additionally, the pressure inside the tube and the temperature of the tube may be maintained above ambient levels for a period of time to allow the polymer tube to be heat set. In one embodiment, the temperature of the deformed tube may be maintained at greater than or equal to the glass transition temperature of the polymer and less than or equal to the melting temperature of the polymer for a selected period to time. The selected period of time may be between about one minute and about two hours, or more narrowly, between about two minutes and about ten minutes. “Heat setting” refers to allowing aligned polymer chains form crystalline structure at an elevated temperature. Crystallization is a time and temperature dependent process, therefore, a period of time may be necessary to allow polymer chains to adopt crystalline structures at a given temperature that are stable in a deformed state of a polymeric material. Heat setting may also be facilitated by tension.
Alternatively, pressure inside the tube may be allowed to decrease while maintaining the temperature of the tube above an ambient temperature prior to complete realignment of the polymer chains. In this case, the polymer tube may be “heat shrunk” which refers to a decrease in the diameter of the tube. The polymer tube may be heat shrunk to a desired diameter. In either case, the polymer tube may be cooled to below the Tg either before or after decreasing the pressure inside of the tube. Cooling the tube helps insure that it maintains the proper shape, size, and length following its formation. Upon cooling the deformed tube retains the length and shape imposed by an inner surface of the mold.
The degree of deformation or expansion may be quantified by a blow-up ratio:
In some embodiments, the blow-up ratio of a polymer tube for use in fabricating an implantable medical device may be between 1 and 10, or more narrowly between 2 and 5. In certain embodiments, the blow-up ratio of a deformed tube for use as an inflatable member may be between 1 and 10, or more narrowly between 3 and 6.
Polymer tube 150 may be heated by heating the gas to a temperature above ambient temperature prior to conveying the gas into polymer tube 150. Alternatively, the polymer tube may be heated by heating the exterior of annular member 160. The increase in pressure inside of polymer tube 150 facilitated by an increase in temperature of the polymer tube cause radial deformation of polymer tube 150, as indicated by an arrow 185.
Furthermore, as indicated above, increasing the temperature of a polymer by heating may facilitate deformation of a polymer, and hence, induction of circumferential polymer chain alignment and modification of the mechanical properties of the polymer. In general, it is desirable to deform a polymer above the Tg of the polymer since the segmental mobility necessary for realignment of polymer chains is extremely limited below the Tg. As a result of the increased segmental mobility, the modulus of a polymer decreases with increased temperature, making the polymer easier to deform. Consequently, the amount of deformation depends on the temperature of a polymeric material. Therefore, it may be necessary for the increase in temperature of a polymer material to be uniform or relatively uniform to achieve uniform or relatively uniform deformation throughout a volume of a polymer material. A more uniform deformation of the tube may also result in a more uniform induced circumferential polymer alignment and induced mechanical properties. In general, the more uniform the enhancement of material properties due to deformation, the more mechanically stable the device is. In particular, localized regions with unfavorable mechanical properties that are susceptible to mechanical failure may be reduced or eliminated by more uniform heating, or by a more uniform increase in the temperature of the polymeric material.
Certain embodiments of a method of fabricating a medical article with uniform or substantially uniform mechanical properties may include heating a polymer tube with a liquid while at least partially immersed in the liquid. It may be advantageous to completely immerse the tube in the liquid to facilitate uniform heating of the tube. The method may further include deforming the tube. The heated and deformed tube may then be used for fabricating an implantable medical device or used as an inflatable member. In some embodiments, the liquid may include a liquid that does not significantly degrade or adversely modify the polymeric material of the tube during the time frame of the heating and/or deformation process. For example, the liquid may include water, alcohols, oils (e.g., vegetable oil), or any liquid that that is not a solvent for or that may swell the polymer material.
In some embodiments, the liquid may heat the polymer tube to greater than or equal to the Tg of the polymer and less than or equal to the Tm, of the polymer. The tube may be immersed in the liquid for a period of time sufficient to heat the volume of the polymer tube uniformly or substantially uniformly throughout the volume of the polymeric material of the tube to a desired temperature. The period of time may be a few seconds to 10 minutes or more narrowly from one to five minutes. As indicated above, in certain embodiments, the tube may be heated with the liquid prior to, contemporaneously with, and/or subsequent to deforming the tube. For instance, it may be advantageous to deform the tube while at least partially immersed in the liquid so that the tube remains at a substantially uniform and constant temperature during deformation. In addition, the temperature of the polymer tube may be maintained to heat set and/or heat shrink the polymer tube during and subsequent to deformation of the tube.
Additionally, deforming the tube may modify mechanical properties of the tube. For instance, deformation may increase the circumferential strength and/or circumferential modulus of the tube. In some embodiments, heating the tube uniformly or substantially uniformly with the liquid may result in a more uniform deformation and modification of mechanical properties of the tube than heating the tube using other methods such as with a gas and/or electrical heating.
In addition, exposure of a polymer to a solvent may also facilitate inducing circumferential polymer chain alignment and modification of the mechanical properties of a polymer. It has been observed that exposing a polymer to a solvent of the polymer induces crystallization in the polymer. The phenomenon may be referred to as solvent-induced crystallization. Some solvents of a polymer tend to induce crystallization because the solvent lowers the crystallization temperature of the polymer. In particular, absorption of a solvent by the polymer tends to decrease the Tg of the polymer. Below the Tg of the polymer no or substantially no crystallization of a polymer tends to occur. Therefore, as a result of a decrease of the Tg, the temperature at which polymer chains may have sufficient mobility to align and crystallize is decreased. Representative solvents that may be used for solvent treatment of polymer tubes include, but are not limited to, water, isopropyl alcohol, and ethanol. For example, water or moisture can be used to increase the crystallization rate of poly(lactic acid) and poly(ethylene terephthalate).
As discussed above, a polymer tube may be heated to facilitate deformation and induction of circumferential polymer chain alignment. The polymer material is heated to above a temperature at which polymer chain alignment may occur, typically the Tg of the polymer. Consequently, solvent-treating a polymer tube may decrease the temperature increase that may be required to facilitate deformation. Since the possibility of degradation of a polymer increases as temperature increase, solvent-treating a polymer tube may be advantageous, particularly for polymers with high Tg's.
Representative methods of treating at least a portion of the tube with a solvent may include, but are not limited to, immersing at least a portion of the tube in the solvent, spraying at least a portion of the tube with the solvent, and/or applying the solvent to at least a portion of the tube. In addition, as indicated above and illustrated in
Furthermore, the polymer tube may be treated with the solvent prior to, contemporaneously with, and/or subsequent to deforming the tube. In one embodiment, the polymer tube may be immersed in the solvent for a period of time to allow for absorption of the solvent and then deformed after removal from the solvent. In some embodiments, the immersion time may be between two minutes and ten minutes, or more narrowly between three minutes and seven minutes. In another embodiment, the polymer tube may be deformed while immersed in the solvent. It may be desirable to deform the polymer tube in the solvent to maintain a constant and uniform or substantially constant and uniform concentration of solvent in the polymer tube. Some solvents may be relatively volatile in temperature ranges of deformation, and therefore, may evaporate from a tube removed from the solvent bath. The evaporation may result in a concentration gradient of the solvent in the polymer tube resulting in nonuniform deformation and material properties in the polymer tube.
In an embodiment, a polymer tube may be deformed after a solvent is sprayed and/or applied to a polymer tube. Alternatively, the solvent may be sprayed on and/or applied to the polymer tube during and/or after deforming the polymer tube. Spraying and/or applying the solvent during and/or after deforming may reduce or prevent a concentration gradient in the polymer tube. Spraying and/or applying the solvent may be desirable for solvents that tend to strongly dissolve the polymer tube. In general, the solvent treatment of the polymer tube should be configured to not significantly degrade the polymer tube during the time frame of the treatment process.
Additionally, the choice of a solvent for solvent treating a polymer tube may depend on the degree of induced crystallization that is desired. As the strength of the solvent increases, the induced crystallization increases. However, a solvent that is too strong may degrade the polymer more than is desired during a time frame of the solvent treatment. The strength of solvent, the time of treatment, and the temperature during deformation are related process parameters. As the strength of the solvent increases, the time required for treatment and the temperature required during deformation decrease.
Therefore, some embodiments of a method for fabricating a medical article may include treating at least a portion of a polymer tube with a solvent capable of inducing crystallization of the polymer. The method may further include deforming the polymer tube. The heated and deformed tube may then be used for fabricating an implantable medical device or used as an inflatable member.
As discussed above, treating the tube with the solvent decreases a crystallization temperature of the polymer. It follows that in some embodiments, treating the polymer tube with the solvent may then decrease a temperature at which the polymer chain alignment can occur. This, in term, facilitates the deformation of the polymer tube. The induced polymer chain alignment, or crystallization, of the polymer may additionally facilitate modifying the mechanical properties of the polymer tube along with the deformation.
As discussed above, radial deformation of a polymer tube may increase circumferential polymer chain alignment with a concomitant increase in properties such as in circumferential strength and modulus. However, the change of polymer properties due to deformation is generally sensitive to deformation rate, and hence, the induced strain rate. As a result, the induced circumferential polymer chain alignment and induced changes in properties depend on the overall rate of deformation of the tube or the overall strain rate induced by an applied stress. For instance, the relative amount of radial and axial deformation and the volumetric uniformity of the deformation depend on the rate of deformation. Deforming a polymer tube by increasing the pressure without adequate control of the rate of deformation tends to result in significant radial and axial deformation as well as volumetrically nonuniform deformation. As a result, higher strain rates applied to a tube tend to impart less circumferential deformation, and hence, polymer chain alignment.
Additionally, a higher strain rate may result in failure of a tube at a smaller diameter than with a lower strain rate. Therefore, deforming at a lower strain rate allows deformation to a larger diameter, and hence, greater induced circumferential polymer chain alignment, without failure.
In general, free or unrestrained deformation with a compressible fluid or gas from an original diameter to a desired diameter may result in undesirably high strain rates. In free or unrestrained deformation, the degree of axial orientation tends to be difficult to control. Furthermore, deformation of a polymer tube with a compressible fluid such as an inert gas (air, nitrogen, oxygen, argon, etc.) may not allow control of the relative degree of radial and axial deformation and of the volumetric uniformity of deformation.
As indicated above, it is desirable to induce a higher degree of radial deformation rather than axial deformation. There is generally less of a need to further induce polymer chain alignment in the axial direction, since, as indicated above, conventionally extruded polymer tubes already possess a significant degree of axial polymer chain alignment. Reducing the degree of axial deformation may increase the degree of induced circumferential strength and modulus for a given amount of deformation. As indicated above, it has been observed that decreasing the rate of deformation of a polymer tube increases the degree of radial deformation and decreases the degree of axial deformation. Therefore, controlling the rate of deformation of a tube to be slower than deformation obtained from, for example, free expansion with a compressible fluid, may provide a relatively high radial deformation and relatively low or no axial deformation. Increasing the degree of radial deformation may also increase the circumferential strength and modulus induced by the deformation. Additionally, slower deformation reduces the possibility of sudden expansion in a local area of weakness of a polymer tube and propagation of expansion from that point.
In some embodiments, the use of an incompressible fluid to deform a polymer tube may allow control over the rate of deformation of the tube. A method for fabricating a medical article may include deforming a polymer tube at least by increasing a pressure inside of the tube with an incompressible or substantially incompressible fluid. The pressure may be increased by conveying the fluid into the tube. For example, the incompressible fluid may be conveyed into a polymer tube as indicated by arrow 115 in
The incompressible fluid may include any fluid that does not significantly degrade or adversely modify the polymeric material of the tube during the time frame of the deformation process. The fluid should also not negatively influence the biocompatibility of the polymer tube. For example, the liquid may include water, alcohols, and other organic liquids.
Some embodiments may include controlling a rate of deformation of the polymer tube by controlling the fluid conveyed into the tube. Increasing the pressure with an incompressible fluid allows control of the deformation of the tube with the rate of fluid addition. In general, the deformation may not be controlled by the rate of fluid addition when a compressible fluid is used. In the case of a compressible fluid, the deformation is determined by the circumferential strength of the polymer tube material. Therefore, in some embodiments, by using an incompressible fluid, the rate of deformation may be controlled to be slower than a rate of deformation with a compressible fluid.
Consequently, the use of an incompressible fluid allows better control over the rate of deformation than deforming with a compressible fluid. As indicated above, controlling, in particular, reducing the rate of deformation of a polymer tube has several advantages. In one embodiment, the rate of deformation of a polymer tube with an incompressible or substantially incompressible fluid may be controlled to result in a higher ratio of radial to axial deformation than with a compressible fluid. Similarly, the rate of deformation with an incompressible fluid may be controlled to reduce or eliminate axial deformation. Therefore, the rate of deformation may be controlled to increase a circumferential strength and/or modulus of the tube more than deforming the tube with a compressible fluid. In addition, the rate of deformation with an incompressible or substantially incompressible fluid may be controlled to reduce or prevent sudden localized deformation of the tube.
As indicated above, controlling deformation rate of a polymer tube has several advantages. In particular, decreasing the deformation rate of a polymer tube can result in higher radial deformation with little or no axial deformation. It follows that a decreased deformation rate can increase the degree of induced circumferential strength and modulus of the polymer tube. In addition, deformation of a uniformly or substantially uniformly heated tube facilitates uniform deformation and formation of a deformed tube with uniform material properties.
However, the use of an incompressible fluid or a liquid as a means of controlling deformation and for uniform heating may have some disadvantages. The exposure of some liquids to a polymer tube during deformation may adversely affect the biocompatibility of a fabricated medical article. For example, water can promote the growth of pyrogens. It may be necessary to remove the water before further processing of a deformed polymer tube after exposure to water in the deformation process. Therefore, it may be desirable to perform a controlled deformation of a polymer tube in a dry or relatively dry environment without exposure of the tube to a liquid.
Fabrication of inflatable members in lobed molds illustrates the advantages of a reduced expansion rate in a dry environment. The deformation in a lobed mold for fabricating inflatable members occurs in stages which results in a lower overall expansion rate than deformation in a conventional or cylindrical mold.
The first stage of a deformation may result in expansion to a minor diameter 424 of mold member 415. A second stage may result in expansion of a tube conforming to surfaces 421 of triply lobed inner bore 420. It has been observed that tubing designed for a circular mold of a given diameter may be deformed beyond a minor diameter without failure when formed in a lobed mold that is designed to give a larger diameter relative to the circular mold. These balloons exhibit a thinner wall and a higher modulus than balloons formed in a conventional mold using free or unrestrained expansion. A 15 percent increase in blow-up ratio has been observed through the use of lobed molds.
Additionally, when lobed molds are used to blow balloons to the same diameter as a conventional circular cross-section mold using the same tubing, additional tension has to be applied when using the lobed mold in order to get the same wall thickness as that obtained using the circular mold. This indicates that the reduced expansion rate in the lobed mold also reduces the amount of axial orientation imparted to the tubing during the tubing expansion process.
In general, the deformation rate of a polymer tube is lower in a lobed mold than in a conventional cylindrical mold. The reduced deformation rate results in a balloon with thinner walls, less axial deformation, more circumferential deformation (imparting a higher circumferential modulus) than a balloon formed in a conventional circular mold. It is desirable to obtain similar reduction in deformation rate for a balloon formed in a conventional cylindrical mold.
Some embodiments of a method for fabricating a medical article in a dry environment may include controlling the deformation of a tube disposed within a cavity with a variable size cross-section. The cavity may be defined by a radially movable surface configured to restrain at least a portion of the deforming tube. The method may further include fabricating an implantable medical device from the deformed tube or using the deformed tube as an inflatable member. The deformation process may be performed without exposing the polymer tube to a liquid, or generally to a wet environment.
In some embodiments, the tube may be deformed by increasing a pressure in the tube. The pressure may be increased, as described above, by conveying a fluid into the tube. The fluid may be an inert gas, such as air, oxygen, nitrogen, and/or argon. In other embodiments, the fluid may be a liquid.
In an embodiment, a polymer tube may be positioned adjacent to the radially movable restraining surfaces. A longitudinal axis of the cavity may be parallel or substantially parallel to a cylindrical axis of the polymer tube. The polymer tube may be uniformly heated prior to deformation. In addition, the tube may be heated contemporaneously with and subsequent to the deformation. As the polymer tube is deformed by an increase in pressure inside the tube, at least a portion of the exterior surface of the tube may make contact with at least a portion of the radially movable restraining surface. In some embodiments, all or substantially all of an outside surface of the polymer tube may be in contact with the restraining surface. The deformation, in particular the deformation rate, of the tube may be controlled by outward radial movement of the restraining surface. The rate of deformation of the polymer tube may be readily controlled by controlling a rate of movement of the restraining surface.
In one embodiment, the surfaces may control deformation by controlling the radial movement of the surfaces directly through adjustment of the cavity to a desired size. The change in the size of the cavity may be continuous or in stages or steps. In other embodiments, the restraining surfaces may exert a constant or variable force on the surface of the deforming tube. The surfaces may move radially outward to allow deformation when the force is less than the force exerted by the deforming tube.
In certain embodiments, a rate of deformation of the polymer tube may be controlled to be slower than a rate of unrestrained or free deformation of the tube. Therefore, the rate of deformation may be controlled to increase the radial deformation and reduce or eliminate axial deformation. Additionally, a rate of deformation of the polymer tube may be controlled to increase a circumferential strength and circumferential modulus of the tube more than an unrestrained or free deformation of the tube. Further, as mentioned above, unrestrained deformation of a polymer tube with a compressible fluid may lead to sudden localized deformation in the tube. Controlling the expansion with a radially movable restraining surface may reduce or eliminate such sudden localized deformation.
In certain embodiments, the polymer tube may be heated prior to, contemporaneously with, and/or subsequent to deformation with a heated gas conveyed into the tube. In addition, the polymer tube may be heated with the restraining surface. The tube is deformed at a temperature greater than or equal to a glass transition temperature of the polymer and less than or equal to a melting temperature of the polymer. In other embodiments, the tube may be deformed at a temperature below the glass transition temperature.
In one embodiment, the movable restraining surface forms a cavity in which the polymer tube may be disposed. The radial cross-section of the cavity may be varied during deformation by movement of the restraining surface. There are various ways of forming a restraining surface for controlling deformation of a polymer tube. In one embodiment, a restraining surface may include at least three surfaces of longitudinal wedge members arranged to form a cavity. The wedge members may be configured to slide in a manner than varies the size of the cavity, such as in a sliding wedge crimper. Another example of a movable restraining surface may include the inside of an iris mechanism. The wedge members or iris may be constructed from a variety of heat conductive materials. Representative materials may include, but are not limited to, stainless steel, beryllium copper, brass, and aluminum.
During the preheating stage illustrated in
When polymer tube 255 has reached a desired temperature, the pressure in the portion of polymer tube 255 is increased by conveying a gas into proximal end 275. The increase in the pressure radially deforms polymer tube 255 to a diameter of opening 295 of iris mechanism 265 so that a surface of polymer tube 255 makes contact with the surface of walls 300 of opening 295. Opening 295 of iris mechanism 265 is slowly increased as indicated by the arrows 305 to allow radial deformation of polymer tube 255. Movable walls 300 control the deformation rate of polymer tube 255 to allow uniform expansion along the length of polymer tube 255.
Certain embodiments of fabricating medical articles such as implantable medical devices and inflatable members may also include deforming a polymer tube within an annular mold member with at least three radially movable restraining members within the annular mold member. The method may further include controlling the deformation of at least a portion of the tube with at least three of the restraining members configured to restrain the deforming tube. The annular mold member may be constructed from polymeric and/or metallic materials. Representative materials may include, but are not limited to, stainless steel, beryllium copper, brass, and aluminum.
In certain embodiments, a tensile force may be applied to the tube to control a degree of axial orientation imparted to the tube during the deformation process. A suitable tensile force may be 0.5 Newtons to 20 Newtons, or more narrowly, 5 Newtons to 15 Newtons.
In some embodiments, the restraining members may be slidably disposed within a wall of the mold member. At least a distal portion of a restraining member may extend outward through an opening in the wall of the mold member out of an outside surface of the annular member. At least a portion of a center portion may extend through an opening in the wall of the annular member. In some embodiments, the distal portion may be configured such that it cannot slide into the opening in the wall. At least a portion of a proximal portion of the restraining member may extend radially into at least a portion of the annular member. A surface of the proximal portion of the restraining member may be configured to make contact with a polymer tube deforming within the annular mold member. The restraining members may also be configured to control the deformation of the tube by exerting an inward radial force that opposes the outward radial deformation of the tube. In one embodiment, the inward radial force may be less than the outward radial force exerted by the deforming tube. The slidably disposed annular members may then slide radially outward. As a result, the rate of deformation of the tube is controlled to be slower than a free or unrestrained deformation. In an alternative embodiment, a distal portion of at least one restraining member may be coupled to an inside surface of the annular mold member.
In one embodiment, the inward radial force exerted by the restraining members may be constant (not vary with radial position of the restraining member), increase as the restraining member slides outward, or decrease as the restraining member slides outward. For example, the force may be exerted by a spring and/or a band coupled to the distal end of the restraining members. For instance, the force exerted by the restraining member may be configured to increase as the restraining member slides outward since the force law of a spring or a band parabolically increases. A constant or nearly constant force may be simulated through the use of a relatively loose or flexible spring. Alternatively, the force exerted by a stiff spring increases steeply as the restraining member slides radially outward. Alternatively, the distal end of the restraining members may be coupled to pressurized pistons. The pistons may be configured to have any functional dependence between force exerted by the restraining member and radial position of the restraining member.
In an alternative embodiment, the restraining members may allow deformation of the tube in a step-wise fashion. The restraining members may be configured to slide radially outward in pre-defined radial increments at a pre-defined rate. The size of the increments and the rate of the steps may be controlled manually or automatically. In one embodiment, the distal end of the restraining member may be configured to be releasably coupled within a series of slots at various radial distances.
Further, the restrained portion of the tube that is controlled may correspond to at least a portion of an outer surface of a selected axial portion of the tube. The selected axial portion may be a proximal portion, a distal portion, and/or from an axial portion to a distal portion. A selected axial portion of the polymer may be controlled by disposing restraining members at and/or proximate to the selected axial portion of the annular mold member.
In one embodiment, a restraining member may extend radially into and longitudinally along at least a portion of a cylindrical axis of the mold member. A restraining member may be parallel or substantially parallel to the cylindrical axis of the mold member. A cross-section of the restraining members may be any of a variety of shapes, for example, rectangular, cylindrical, conical, etc.
Furthermore, the restraining members may control and/or restrain the deformation of the tube in a radially symmetric manner along the same axial portion of an annular mold member. For example, three restraining members may be radially spaced equally or approximately equally apart, in this case, 120°.
In some embodiments, a rate of deformation of the polymer tube is controlled to be slower than a rate of unrestrained deformation of the tube. A slower rate of deformation may reduce or prevent failure of the tube during deformation. A slower rate of deformation may allow deformation to a desired diameter without rupturing. Deformation to a larger diameter is preferable due to the larger degree of circumferential orientation induced. Consequently, a rate of deformation of the polymer tube may be controlled to increase a circumferential strength and circumferential modulus of the tube more than a free or unrestrained deformation of the tube. In addition, a slower rate of deformation may reduce or eliminate axial deformation of the tube.
In one embodiment, the restraining members may be configured to control the expansion of the tube until the outside surface of the deformed tube contacts an inner surface of the mold member. Alternatively, when the tube has deformed to a desired degree, the force restraining the restraining members may be reduced or eliminated. In addition, the restraining members may be slid radially outward such that no portion of the restraining member is within the annular member.
In some embodiments, after deforming the tube to a desired diameter, the radial cross-section of a deformed tube may be distorted. To restore a cylindrical or substantially circular radial-cross-section, pressure and optionally heat may be applied within the deformed polymer tube. After the desired degree of deformation has been achieved, the deformed tube may then be allowed to heat set and cool.
Numerous variations may be included in a mold member with restraining members. For example, restraining members may also be included in mold members configured to fabricate inflatable members with sections having different diameters, as illustrated in
Additional embodiments of fabricating a medical article with controlled deformation may include deforming a polymer tube in a staged mold apparatus. The method may include allowing a polymer tube to deform in a first stage within a chamber initially defined by a first restraining surface of an inner mold member. The inner mold member may be slidably disposed at least in part within an outer mold member with a second restraining surface initially in contact with an outer surface of the inner mold member. In one embodiment, the deformed tube may be allowed to further deform in a second stage within a section of the chamber defined by at least a portion of the second restraining surface after sliding the inner mold member out of the section of the chamber.
Prior to the first stage of deformation, the tube may have a diameter less than the diameter of the chamber. The tube may be deformed, as described above, by increasing the pressure inside of the tube. In addition, the tube may be heated. In an embodiment, the tube may be deformed until at least a portion of the outside surface of the tube conforms to and is restrained by the first restraining surface. The tube may be heated by conveying gas into the tube. The tube may also be heated by the inner mold member. In one embodiment, the tube may be heated prior to, during, and after deforming the tube with the applied pressure. In certain embodiments, the deformed tube may be allowed to heat set after the first stage of deformation prior to deforming the tube in a second stage. The tube may be heat set while still under pressure. In one embodiment, the tube may be allowed to cool between the stages. The application of heat and pressure may be reduced or eliminated for a period of time between the first stage and the second stage.
In some embodiments, the deformed tube may be deformed further in a second stage. A tube deformed in a first stage may be allowed to deform within a section of the chamber defined by at least a portion of the second restraining surface after sliding the inner mold member out of the section of the chamber. The section of the chamber defined by the second restraining surface may be formed by sliding the inner mold member out of the section. Pressure and heat applied to the inside of the tube may cause further deformation of the tube until it is restrained by the second restraining surface.
Deforming a tube from a first to a second diameter in at least two stages may have several advantages over deforming the tube in a single unrestrained deformation to the second diameter. In some embodiments, the overall rate of deformation in at least two stages may be slower than a single stage unrestrained deformation of the tube from a first diameter to a second diameter. As indicated above, a slower deformation rate may reduce or prevent failure of the tube during deformation. Additionally, deforming the tube in at least two stages increases a circumferential strength and circumferential modulus of the tube more than a single stage unrestrained deformation of the tube from a first diameter to a second diameter. Deforming the tube in at least two stages also reduces or eliminates axial deformation of the tube.
Additionally, a method of fabricating an inflatable medical device may further include fabricating adjustable length inflatable members as disclosed in U.S. Patent Publication No. 20020125617. In addition, inflatable members with sections having different diameters may also be fabricated by deformation of a polymer tube in stages.
Other embodiments of the method may include deforming the polymer in more than two stages. In one embodiment, an additional third stage may include allowing the tube to deform within a second section of the chamber, the second section defined by at least a portion of a third restraining surface after sliding the outer mold member out of the second section of the chamber. The outer mold member may be slidably disposed at least in part within a second outer mold member having the third restraining surface. In one embodiment, the second section may be at least a part of or greater than the section in which the second stage of the deformation was performed.
As illustrated in
Furthermore, a staged mold may be used to fabricate expanded tubes of the same length, but with different diameters.
Some embodiments of staged deformation may include an inner mold member with a circular or substantially circular cross-section, similar to that shown in
In an embodiment, a tube may be deformed in a first stage in an inner mold member with a noncircular cross-section. The tube may then be deformed in a mold with a circular cross-section by sliding the first mold member out of a section of the chamber.
Example: Wet Deformation
Some embodiments of the present invention are illustrated by the following Example. The Example is being given by way of illustration only and not by way of limitation. The Example illustrates wet deformation of a polymer tube. The parameters and data are not to be construed to unduly limit the scope of the embodiments of the invention.
The sample was a poly(L-lactic acid) tube with 0.09/0.065 (0.09 in outside diameter (OD) and 0.065 in inside diameter (ID)). The tube was deformed in a 0.136 in glass mold immersed in a circulating water bath at 55° C. One end of the tube was sealed by heating the end of the tubing with an air box at 225° F. and clamping it with pliers when it softened. The other end of the tube was connected to a water pump. The air was pumped out and the water was pumped in. The tubing was placed in the glass mold. The tube in the mold was immersed in the heated water bath for 10 minutes. One end of the end of the glass mold was left out of the water. The sealed end of the tubing was kept inside the glass mold
The pressure was slowly increased in the tube after 10 minutes in the water bath. The tube was pressurized with a 20/30 indeflator. One end of the glass mold was held against the bottom of the water tank to keep the tubing from leaving the mold during the initial expansion. The tube was deformed until the deformed tubing was at the water line on the mold. The indeflator pressurized the tube to approximately 14 atm.
The tubing was left pressurized in the hot water for 4 minutes. The tube and mold were then removed from the hot water and placed in a room temperature water bath for 1 minute. The pressure was released after one minute. The tube was removed from the mold. The sealed end of the tube was cut and air was blown through the tubing to dry it.
The deformed tubing had a 0.006 in wall thickness and an OD of 0.136 in. This gives a blow-up ratio of 2.1 (110% radial expansion) and an area draw down ratio of 1.21 (only 20% axial elongation). Area draw down ratio is defined as the cross-sectional area of tubing divided by the cross-sectional area of expanded tubing.
In addition, samples were prepared by deforming the tubes with a gas. The tubes were deformed as illustrated and described in reference to
Blow pressure—334 psi
Preheat time—15 sec
Temperature 225 F
Nozzle speed=2 mm/sec (Group 1-3)
Nozzle speed=5 mm/sec (Group 4)
Nozzle speed refers to speed of a heating nozzle that travels along the length of the mold to heat the mold and tubing. Only a section of the tubing is heated at any given time. Nozzle speed determines the rate of heating for a given section The slower the nozzle speed, the higher the rate of heating for a heated section. Samples 1, 3, and 4 were 100% poly(L-lactic acid) tubes and sample 2 was an 80/20 blend of poly(L-lactic acid) and poly(trimethylene carbonate).
A summary of the results of the gas-deformed and water-deformed samples are shown in Table 1. Samples 1 to 4 correspond to tubes deformed with gas and sample 5 was deformed with liquid. Samples blown using hot air and air pressure were compared with the water expanded samples under a birefringence lamp to examine the stress distribution. The water expanded tubing had a more uniform stress distribution indicating a more uniform deformation.
TABLE 1 Summary of deformation runs. Pre-Def. Def. Mold Pre-def. Post-def. Wall Thick- Wall Thick- Group OD (in) OD/ID (in) OD/ID (in) ness (in) ness (in) 1 .094 .066/.039 .0935/.0845 0.0135 .0045 2 .094 .066/.039 .0935/.085 0.0135 .0043 3 (1) .1365 .066/.039 .1355/.1305 0.0135 .0025 3 (2) .1365 .066/.039 .1347/.13 0.0135 .0025 4 .1365 .066/.039 .136/.132-.133 0.0135 .00225 5 .1365 .090/.065 .136/.133 0.0135 .006
Example: Optical Micrographs of Stents
As indicated above, a polymeric stent with induced polymer chain alignment may be more resistant to cracking during use, including crimping, delivery, and deployment.
While particular embodiments of the present invention have been shown and described, it will be obvious to those skilled in the art that changes and modifications can be made without departing from this invention in its broader aspects. Therefore, the appended claims are to encompass within their scope all such changes and modifications as fall within the true spirit and scope of this invention.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US3636956||May 13, 1970||Jan 25, 1972||Ethicon Inc||Polylactide sutures|
|US3687135||Sep 15, 1969||Aug 29, 1972||Evgeny Mikhailovich Savitsky||Magnesium-base alloy for use in bone surgery|
|US3839743||Oct 15, 1973||Oct 8, 1974||A Schwarcz||Method for maintaining the normal integrity of blood|
|US3900632||Apr 3, 1972||Aug 19, 1975||Kimberly Clark Co||Laminate of tissue and random laid continuous filament web|
|US4104410||Sep 9, 1976||Aug 1, 1978||Malecki George J||Processing of green vegetables for color retention in canning|
|US4110497||Jul 2, 1976||Aug 29, 1978||Snyder Manufacturing Co., Ltd.||Striped laminate and method and apparatus for making same|
|US4321711||Oct 12, 1979||Mar 30, 1982||Sumitomo Electric Industries, Ltd.||Vascular prosthesis|
|US4346028||Nov 24, 1980||Aug 24, 1982||Monsanto Company||Asbestiform crystalline calcium sodium or lithium phosphate, preparation and compositions|
|US4547416||Mar 7, 1984||Oct 15, 1985||Metal Box Limited||Thermoplastics articles and method and apparatus for making them|
|US4596574||May 14, 1984||Jun 24, 1986||The Regents Of The University Of California||Biodegradable porous ceramic delivery system for bone morphogenetic protein|
|US4599085||Feb 1, 1984||Jul 8, 1986||Neodontics, Inc.||Bone implant member for prostheses and bone connecting elements and process for the production thereof|
|US4612009||Jun 11, 1985||Sep 16, 1986||Ceskoslovenska Akademie Ved||Biodegradable implant and a method for preparation thereof|
|US4633873||Apr 26, 1984||Jan 6, 1987||American Cyanamid Company||Surgical repair mesh|
|US4656083||Mar 11, 1985||Apr 7, 1987||Washington Research Foundation||Plasma gas discharge treatment for improving the biocompatibility of biomaterials|
|US4698196||Dec 24, 1985||Oct 6, 1987||Xerox Corporation||Method and apparatus for extruding creaseless thin walled tubes|
|US4702884||Jul 3, 1986||Oct 27, 1987||The United States Of America As Represented By The Secretary Of The Navy||Glass-lined pipes|
|US4718907||Jun 20, 1985||Jan 12, 1988||Atrium Medical Corporation||Vascular prosthesis having fluorinated coating with varying F/C ratio|
|US4722335||Oct 20, 1986||Feb 2, 1988||Vilasi Joseph A||Expandable endotracheal tube|
|US4723549||Sep 18, 1986||Feb 9, 1988||Wholey Mark H||Method and apparatus for dilating blood vessels|
|US4732152||Dec 5, 1985||Mar 22, 1988||Medinvent S.A.||Device for implantation and a method of implantation in a vessel using such device|
|US4733665||Nov 7, 1985||Mar 29, 1988||Expandable Grafts Partnership||Expandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft|
|US4739762||Nov 3, 1986||Apr 26, 1988||Expandable Grafts Partnership||Expandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft|
|US4740207||Sep 10, 1986||Apr 26, 1988||Kreamer Jeffry W||Intralumenal graft|
|US4743252||Jan 13, 1986||May 10, 1988||Corvita Corporation||Composite grafts|
|US4768507||Aug 31, 1987||Sep 6, 1988||Medinnovations, Inc.||Intravascular stent and percutaneous insertion catheter system for the dilation of an arterial stenosis and the prevention of arterial restenosis|
|US4776337||Jun 26, 1986||Oct 11, 1988||Expandable Grafts Partnership||Expandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft|
|US4800882||Mar 13, 1987||Jan 31, 1989||Cook Incorporated||Endovascular stent and delivery system|
|US4816339||Apr 28, 1987||Mar 28, 1989||Baxter International Inc.||Multi-layered poly(tetrafluoroethylene)/elastomer materials useful for in vivo implantation|
|US4818559||Jul 29, 1986||Apr 4, 1989||Sumitomo Chemical Company, Limited||Method for producing endosseous implants|
|US4850999||May 26, 1981||Jul 25, 1989||Institute Fur Textil-Und Faserforschung Of Stuttgart||Flexible hollow organ|
|US4877030||May 31, 1988||Oct 31, 1989||Andreas Beck||Device for the widening of blood vessels|
|US4878906||Jun 6, 1988||Nov 7, 1989||Servetus Partnership||Endoprosthesis for repairing a damaged vessel|
|US4879135||Jul 18, 1988||Nov 7, 1989||University Of Medicine And Dentistry Of New Jersey||Drug bonded prosthesis and process for producing same|
|US4886062||Oct 19, 1987||Dec 12, 1989||Medtronic, Inc.||Intravascular radially expandable stent and method of implant|
|US4902289||Aug 9, 1988||Feb 20, 1990||Massachusetts Institute Of Technology||Multilayer bioreplaceable blood vessel prosthesis|
|US4957687||Nov 7, 1984||Sep 18, 1990||Bulent Akman||Method for making profiled plastic tubes such as corrugated tubes|
|US4977901||Apr 6, 1990||Dec 18, 1990||Minnesota Mining And Manufacturing Company||Article having non-crosslinked crystallized polymer coatings|
|US4987025||Jul 19, 1988||Jan 22, 1991||Mitsui Petrochemical Industries, Ltd.||Inflation film of ultrahigh molecular weight polyethylene|
|US4994298||Apr 18, 1990||Feb 19, 1991||Biogold Inc.||Method of making a biocompatible prosthesis|
|US5019090||Sep 1, 1988||May 28, 1991||Corvita Corporation||Radially expandable endoprosthesis and the like|
|US5028597||Apr 13, 1990||Jul 2, 1991||Agency Of Industrial Science And Technology||Antithrombogenic materials|
|US5059211||Jun 25, 1987||Oct 22, 1991||Duke University||Absorbable vascular stent|
|US5062829||Mar 16, 1990||Nov 5, 1991||Carter Holt Harvey Plastic Products Group Limited||Relates to devices for administering a substance such as a drug or chemical or the like|
|US5084065||Jul 10, 1989||Jan 28, 1992||Corvita Corporation||Reinforced graft assembly|
|US5085629||Sep 27, 1989||Feb 4, 1992||Medical Engineering Corporation||Biodegradable stent|
|US5087394||Nov 9, 1989||Feb 11, 1992||Scimed Life Systems, Inc.||Method for forming an inflatable balloon for use in a catheter|
|US5100429||Oct 20, 1989||Mar 31, 1992||C. R. Bard, Inc.||Endovascular stent and delivery system|
|US5104410||Oct 22, 1990||Apr 14, 1992||Intermedics Orthopedics, Inc||Surgical implant having multiple layers of sintered porous coating and method|
|US5108416||Feb 13, 1990||Apr 28, 1992||C. R. Bard, Inc.||Stent introducer system|
|US5108417||Sep 14, 1990||Apr 28, 1992||Interface Biomedical Laboratories Corp.||Anti-turbulent, anti-thrombogenic intravascular stent|
|US5108755||Apr 27, 1989||Apr 28, 1992||Sri International||Biodegradable composites for internal medical use|
|US5112457||Jul 23, 1990||May 12, 1992||Case Western Reserve University||Process for producing hydroxylated plasma-polymerized films and the use of the films for enhancing the compatiblity of biomedical implants|
|US5116365||Feb 22, 1991||May 26, 1992||Cordis Corporation||Stent apparatus and method for making|
|US5123917||Apr 27, 1990||Jun 23, 1992||Lee Peter Y||Expandable intraluminal vascular graft|
|US5147302 *||Apr 21, 1989||Sep 15, 1992||Scimed Life Systems, Inc.||Method of shaping a balloon of a balloon catheter|
|US5156623||Apr 5, 1991||Oct 20, 1992||Olympus Optical Co., Ltd.||Sustained release material and method of manufacturing the same|
|US5163951||Mar 27, 1992||Nov 17, 1992||Corvita Corporation||Mesh composite graft|
|US5163952||Sep 14, 1990||Nov 17, 1992||Michael Froix||Expandable polymeric stent with memory and delivery apparatus and method|
|US5163958||Aug 13, 1991||Nov 17, 1992||Cordis Corporation||Carbon coated tubular endoprosthesis|
|US5167614||Oct 29, 1991||Dec 1, 1992||Medical Engineering Corporation||Prostatic stent|
|US5192311||Aug 13, 1990||Mar 9, 1993||Angeion Corporation||Medical implant and method of making|
|US5197977||Apr 30, 1992||Mar 30, 1993||Meadox Medicals, Inc.||Drug delivery collagen-impregnated synthetic vascular graft|
|US5234456||May 7, 1992||Aug 10, 1993||Pfizer Hospital Products Group, Inc.||Hydrophilic stent|
|US5234457||Oct 9, 1991||Aug 10, 1993||Boston Scientific Corporation||Impregnated stent|
|US5236447||Jun 28, 1991||Aug 17, 1993||Nissho Corporation||Artificial tubular organ|
|US5279594||May 23, 1990||Jan 18, 1994||Jackson Richard R||Intubation devices with local anesthetic effect for medical use|
|US5282860||Oct 8, 1992||Feb 1, 1994||Olympus Optical Co., Ltd.||Stent tube for medical use|
|US5289831||Apr 21, 1992||Mar 1, 1994||Vance Products Incorporated||Surface-treated stent, catheter, cannula, and the like|
|US5290271||Jul 29, 1993||Mar 1, 1994||Jernberg Gary R||Surgical implant and method for controlled release of chemotherapeutic agents|
|US5306286||Feb 1, 1991||Apr 26, 1994||Duke University||Absorbable stent|
|US5306294||Aug 5, 1992||Apr 26, 1994||Ultrasonic Sensing And Monitoring Systems, Inc.||Stent construction of rolled configuration|
|US5328471||Aug 4, 1993||Jul 12, 1994||Endoluminal Therapeutics, Inc.||Method and apparatus for treatment of focal disease in hollow tubular organs and other tissue lumens|
|US5330500||Oct 17, 1991||Jul 19, 1994||Song Ho Y||Self-expanding endovascular stent with silicone coating|
|US5342348||Dec 4, 1992||Aug 30, 1994||Kaplan Aaron V||Method and device for treating and enlarging body lumens|
|US5342395||Jan 13, 1992||Aug 30, 1994||American Cyanamid Co.||Absorbable surgical repair devices|
|US5342621||Sep 15, 1992||Aug 30, 1994||Advanced Cardiovascular Systems, Inc.||Antithrombogenic surface|
|US5356433||Nov 3, 1993||Oct 18, 1994||Cordis Corporation||Biocompatible metal surfaces|
|US5383925||Sep 14, 1992||Jan 24, 1995||Meadox Medicals, Inc.||Three-dimensional braided soft tissue prosthesis|
|US5385580||Sep 21, 1992||Jan 31, 1995||Meadox Medicals, Inc.||Self-supporting woven vascular graft|
|US5389106||Oct 29, 1993||Feb 14, 1995||Numed, Inc.||Impermeable expandable intravascular stent|
|US5399666||Apr 21, 1994||Mar 21, 1995||E. I. Du Pont De Nemours And Company||Easily degradable star-block copolymers|
|US5423885||Jul 14, 1993||Jun 13, 1995||Advanced Cardiovascular Systems, Inc.||Stent capable of attachment within a body lumen|
|US5441515||Apr 23, 1993||Aug 15, 1995||Advanced Cardiovascular Systems, Inc.||Ratcheting stent|
|US5443458||Dec 3, 1993||Aug 22, 1995||Advanced Cardiovascular Systems, Inc.||Multilayered biodegradable stent and method of manufacture|
|US5443500||Apr 8, 1994||Aug 22, 1995||Advanced Cardiovascular Systems, Inc.||Intravascular stent|
|US5455040||Nov 19, 1992||Oct 3, 1995||Case Western Reserve University||Anticoagulant plasma polymer-modified substrate|
|US5464650||Apr 26, 1993||Nov 7, 1995||Medtronic, Inc.||Intravascular stent and method|
|US5500013||Jan 13, 1995||Mar 19, 1996||Scimed Life Systems, Inc.||Biodegradable drug delivery vascular stent|
|US5502158||Sep 22, 1992||Mar 26, 1996||Ecopol, Llc||Degradable polymer composition|
|US5514379||Aug 7, 1992||May 7, 1996||The General Hospital Corporation||Hydrogel compositions and methods of use|
|US5527337||Feb 22, 1994||Jun 18, 1996||Duke University||Bioabsorbable stent and method of making the same|
|US5545408||Oct 19, 1992||Aug 13, 1996||Peptide Technology Limited||Biocompatible implant for the timing of ovulation in mares|
|US5554120||Jul 25, 1994||Sep 10, 1996||Advanced Cardiovascular Systems, Inc.||Polymer blends for use in making medical devices including catheters and balloons for dilatation catheters|
|US5556413||Mar 11, 1994||Sep 17, 1996||Advanced Cardiovascular Systems, Inc.||Coiled stent with locking ends|
|US5578046||May 12, 1995||Nov 26, 1996||United States Surgical Corporation||Composite bioabsorbable materials and surgical articles made thereform|
|US5578073||Sep 16, 1994||Nov 26, 1996||Ramot Of Tel Aviv University||Thromboresistant surface treatment for biomaterials|
|US5591199||Jun 7, 1995||Jan 7, 1997||Porter; Christopher H.||Curable fiber composite stent and delivery system|
|US5591607||Jun 6, 1995||Jan 7, 1997||Lynx Therapeutics, Inc.||Oligonucleotide N3→P5' phosphoramidates: triplex DNA formation|
|US5593403||Sep 14, 1994||Jan 14, 1997||Scimed Life Systems Inc.||Method for modifying a stent in an implanted site|
|US5593434||Jun 7, 1995||Jan 14, 1997||Advanced Cardiovascular Systems, Inc.||Stent capable of attachment within a body lumen|
|US5599301||Nov 22, 1993||Feb 4, 1997||Advanced Cardiovascular Systems, Inc.||Motor control system for an automatic catheter inflation system|
|US5599922||Mar 18, 1994||Feb 4, 1997||Lynx Therapeutics, Inc.||Oligonucleotide N3'-P5' phosphoramidates: hybridization and nuclease resistance properties|
|US5605696||Mar 30, 1995||Feb 25, 1997||Advanced Cardiovascular Systems, Inc.||Drug loaded polymeric material and method of manufacture|
|US5607442||Nov 13, 1995||Mar 4, 1997||Isostent, Inc.||Stent with improved radiopacity and appearance characteristics|
|US5607467||Jun 23, 1993||Mar 4, 1997||Froix; Michael||Expandable polymeric stent with memory and delivery apparatus and method|
|US5618299||Aug 8, 1995||Apr 8, 1997||Advanced Cardiovascular Systems, Inc.||Ratcheting stent|
|US5628786||May 12, 1995||May 13, 1997||Impra, Inc.||Radially expandable vascular graft with resistance to longitudinal compression and method of making same|
|US5629077||Jun 27, 1994||May 13, 1997||Advanced Cardiovascular Systems, Inc.||Biodegradable mesh and film stent|
|US5631135||Jun 6, 1995||May 20, 1997||Lynx Therapeutics, Inc.||Oligonucleotide N3'→P5' phosphoramidates: hybridization and nuclease resistance properties|
|US5632771||Jan 25, 1995||May 27, 1997||Cook Incorporated||Flexible stent having a pattern formed from a sheet of material|
|US5632840||Jun 6, 1995||May 27, 1997||Advanced Cardiovascular System, Inc.||Method of making metal reinforced polymer stent|
|US5637113||Dec 13, 1994||Jun 10, 1997||Advanced Cardiovascular Systems, Inc.||Polymer film for wrapping a stent structure|
|US5649977||Sep 22, 1994||Jul 22, 1997||Advanced Cardiovascular Systems, Inc.||Metal reinforced polymer stent|
|US5667767||Jul 27, 1995||Sep 16, 1997||Micro Therapeutics, Inc.||Compositions for use in embolizing blood vessels|
|US5667796||Jun 5, 1996||Sep 16, 1997||Otten; Klaus||Method for producing ceramic implant materials, preferably ceramic implant materials including hydroxyl apatite|
|US5670161||May 28, 1996||Sep 23, 1997||Healy; Kevin E.||Biodegradable stent|
|US5670558||Jul 6, 1995||Sep 23, 1997||Terumo Kabushiki Kaisha||Medical instruments that exhibit surface lubricity when wetted|
|US5693085||Apr 26, 1995||Dec 2, 1997||Scimed Life Systems, Inc.||Stent with collagen|
|US5700286||Aug 22, 1996||Dec 23, 1997||Advanced Cardiovascular Systems, Inc.||Polymer film for wrapping a stent structure|
|US5707385||Nov 16, 1994||Jan 13, 1998||Advanced Cardiovascular Systems, Inc.||Drug loaded elastic membrane and method for delivery|
|US5711763||Jun 30, 1995||Jan 27, 1998||Tdk Corporation||Composite biological implant of a ceramic material in a metal substrate|
|US5716981||Jun 7, 1995||Feb 10, 1998||Angiogenesis Technologies, Inc.||Anti-angiogenic compositions and methods of use|
|US5725549||Sep 12, 1996||Mar 10, 1998||Advanced Cardiovascular Systems, Inc.||Coiled stent with locking ends|
|US5726297||Jun 5, 1995||Mar 10, 1998||Lynx Therapeutics, Inc.||Oligodeoxyribonucleotide N3' P5' phosphoramidates|
|US5728751||Nov 25, 1996||Mar 17, 1998||Meadox Medicals, Inc.||Bonding bio-active materials to substrate surfaces|
|US5733326||May 28, 1996||Mar 31, 1998||Cordis Corporation||Composite material endoprosthesis|
|US5733330||Jan 13, 1997||Mar 31, 1998||Advanced Cardiovascular Systems, Inc.||Balloon-expandable, crush-resistant locking stent|
|US5733564||Apr 12, 1994||Mar 31, 1998||Leiras Oy||Method of treating endo-osteal materials with a bisphosphonate solution|
|US5733925||Oct 28, 1996||Mar 31, 1998||Neorx Corporation||Therapeutic inhibitor of vascular smooth muscle cells|
|US5741881||Nov 25, 1996||Apr 21, 1998||Meadox Medicals, Inc.||Process for preparing covalently bound-heparin containing polyurethane-peo-heparin coating compositions|
|US5756457||May 5, 1995||May 26, 1998||Genetics Institute, Inc.||Neural regeneration using human bone morphogenetic proteins|
|US5756476||Jan 26, 1994||May 26, 1998||The United States Of America As Represented By The Department Of Health And Human Services||Inhibition of cell proliferation using antisense oligonucleotides|
|US5765682||Jun 24, 1996||Jun 16, 1998||Menlo Care, Inc.||Restrictive package for expandable or shape memory medical devices and method of preventing premature change of same|
|US5766204||Sep 12, 1997||Jun 16, 1998||Metastent Incorporated||Curable fiber composite stent and delivery system|
|US5766239||Oct 3, 1997||Jun 16, 1998||Advanced Cardiovascular Systems, Inc.||Balloon-expandable, crush resistant locking stent and method of loading the same|
|US5766710||Jun 19, 1996||Jun 16, 1998||Advanced Cardiovascular Systems, Inc.||Biodegradable mesh and film stent|
|US5769883||Nov 21, 1995||Jun 23, 1998||Scimed Life Systems, Inc.||Biodegradable drug delivery vascular stent|
|US5780807||Jan 15, 1997||Jul 14, 1998||Advanced Cardiovascular Systems, Inc.||Method and apparatus for direct laser cutting of metal stents|
|US5800516||Aug 8, 1996||Sep 1, 1998||Cordis Corporation||Deployable and retrievable shape memory stent/tube and method|
|US5811447||May 25, 1995||Sep 22, 1998||Neorx Corporation||Therapeutic inhibitor of vascular smooth muscle cells|
|US5824049||Oct 31, 1996||Oct 20, 1998||Med Institute, Inc.||Coated implantable medical device|
|US5830178||Oct 11, 1996||Nov 3, 1998||Micro Therapeutics, Inc.||Methods for embolizing vascular sites with an emboilizing composition comprising dimethylsulfoxide|
|US5830461||Nov 8, 1996||Nov 3, 1998||University Of Pittsburgh Of The Commonwealth System Of Higher Education||Methods for promoting wound healing and treating transplant-associated vasculopathy|
|US5830879||Oct 2, 1995||Nov 3, 1998||St. Elizabeth's Medical Center Of Boston, Inc.||Treatment of vascular injury using vascular endothelial growth factor|
|US5833651||Nov 8, 1996||Nov 10, 1998||Medtronic, Inc.||Therapeutic intraluminal stents|
|US5834582||Feb 20, 1996||Nov 10, 1998||Chronopol, Inc.||Degradable polymer composition|
|US5836962||Jan 22, 1997||Nov 17, 1998||Schneider (Europe) Ag||Endoprosthesis|
|US5837313||Jun 13, 1996||Nov 17, 1998||Schneider (Usa) Inc||Drug release stent coating process|
|US5837835||Jun 6, 1995||Nov 17, 1998||Lynx Therapeutics, Inc.||Oligonucleotide N3'-P5' phosphoramidates: hybridization and nuclease resistance properties|
|US5840083||Nov 15, 1996||Nov 24, 1998||F.B. Rice & Co.||Implant device having biocompatiable membrane coating|
|US5851508||Feb 14, 1997||Dec 22, 1998||Microtherapeutics, Inc.||Compositions for use in embolizing blood vessels|
|US5853408||Jun 1, 1995||Dec 29, 1998||Advanced Cardiovascular Systems, Inc.||In-vivo modification of the mechanical properties of surgical devices|
|US5854207||Feb 23, 1998||Dec 29, 1998||Stryker Corporation||Compositions and therapeutic methods using morphogenic proteins and stimulatory factors|
|US5855612||May 10, 1996||Jan 5, 1999||Ohta Inc.||Biocompatible titanium implant|
|US5855618||Sep 13, 1996||Jan 5, 1999||Meadox Medicals, Inc.||Polyurethanes grafted with polyethylene oxide chains containing covalently bonded heparin|
|US5858746||Jan 25, 1995||Jan 12, 1999||Board Of Regents, The University Of Texas System||Gels for encapsulation of biological materials|
|US5865814||Aug 6, 1997||Feb 2, 1999||Medtronic, Inc.||Blood contacting medical device and method|
|US5868781||Oct 22, 1996||Feb 9, 1999||Scimed Life Systems, Inc.||Locking stent|
|US5873904||Feb 24, 1997||Feb 23, 1999||Cook Incorporated||Silver implantable medical device|
|US5874101||Apr 14, 1997||Feb 23, 1999||Usbiomaterials Corp.||Bioactive-gel compositions and methods|
|US5874109||Sep 4, 1997||Feb 23, 1999||The Trustees Of The University Of Pennsylvania||Incorporation of biological molecules into bioactive glasses|
|US5874165||May 27, 1997||Feb 23, 1999||Gore Enterprise Holdings, Inc.||Materials and method for the immobilization of bioactive species onto polymeric subtrates|
|US5876743||Sep 22, 1997||Mar 2, 1999||Den-Mat Corporation||Biocompatible adhesion in tissue repair|
|US5877263||Nov 25, 1996||Mar 2, 1999||Meadox Medicals, Inc.||Process for preparing polymer coatings grafted with polyethylene oxide chains containing covalently bonded bio-active agents|
|US5879713||Jan 23, 1997||Mar 9, 1999||Focal, Inc.||Targeted delivery via biodegradable polymers|
|US5888533||Nov 21, 1997||Mar 30, 1999||Atrix Laboratories, Inc.||Non-polymeric sustained release delivery system|
|US5891192||May 22, 1997||Apr 6, 1999||The Regents Of The University Of California||Ion-implanted protein-coated intralumenal implants|
|US5891386||Apr 25, 1997||Apr 6, 1999||Medtronic, Inc.||Method for making catheter balloons|
|US5897955||Aug 21, 1998||Apr 27, 1999||Gore Hybrid Technologies, Inc.||Materials and methods for the immobilization of bioactive species onto polymeric substrates|
|US5906759||Dec 26, 1996||May 25, 1999||Medinol Ltd.||Stent forming apparatus with stent deforming blades|
|US5914182||Jun 3, 1996||Jun 22, 1999||Gore Hybrid Technologies, Inc.||Materials and methods for the immobilization of bioactive species onto polymeric substrates|
|US5916870||Sep 22, 1998||Jun 29, 1999||Stryker Corporation||Compositions and therapeutic methods using morphogenic proteins and stimulatory factors|
|US5922005||Aug 21, 1998||Jul 13, 1999||Medinol Ltd.||Stent fabrication method|
|US5942209||Nov 3, 1997||Aug 24, 1999||Focal, Inc.||Method of local radiotherapy by polymerizing a material in vivo to form a hydrogel|
|US5948428||Dec 6, 1996||Sep 7, 1999||Stryker Corporation||Compositions and therapeutic methods using morphogenic proteins and stimulatory factors|
|US5954744||Jun 26, 1997||Sep 21, 1999||Quanam Medical Corporation||Intravascular stent|
|US5957975||Dec 15, 1997||Sep 28, 1999||The Cleveland Clinic Foundation||Stent having a programmed pattern of in vivo degradation|
|US5965720||Mar 20, 1995||Oct 12, 1999||Lynx Therapeutics, Inc.||Oligonucleotide N3'→P5' phosphoramidates|
|US5971954||Jan 29, 1997||Oct 26, 1999||Rochester Medical Corporation||Method of making catheter|
|US5976182||Jun 15, 1998||Nov 2, 1999||Advanced Cardiovascular Systems, Inc.||Balloon-expandable, crush-resistant locking stent and method of loading the same|
|US5980564||Aug 1, 1997||Nov 9, 1999||Schneider (Usa) Inc.||Bioabsorbable implantable endoprosthesis with reservoir|
|US5980928||Jul 29, 1997||Nov 9, 1999||Terry; Paul B.||Implant for preventing conjunctivitis in cattle|
|US5980972||Sep 22, 1997||Nov 9, 1999||Schneider (Usa) Inc||Method of applying drug-release coatings|
|US5981568||Mar 31, 1997||Nov 9, 1999||Neorx Corporation||Therapeutic inhibitor of vascular smooth muscle cells|
|US5986169||Dec 31, 1997||Nov 16, 1999||Biorthex Inc.||Porous nickel-titanium alloy article|
|US5997468||Aug 4, 1997||Dec 7, 1999||Medtronic, Inc.||Intraluminal drug eluting prosthesis method|
|US6010445||Nov 12, 1997||Jan 4, 2000||Implant Sciences Corporation||Radioactive medical device and process|
|US6015541||Nov 3, 1997||Jan 18, 2000||Micro Therapeutics, Inc.||Radioactive embolizing compositions|
|US6042875||Mar 2, 1999||Mar 28, 2000||Schneider (Usa) Inc.||Drug-releasing coatings for medical devices|
|US6048964||Dec 12, 1995||Apr 11, 2000||Stryker Corporation||Compositions and therapeutic methods using morphogenic proteins and stimulatory factors|
|US6051648||Jan 13, 1999||Apr 18, 2000||Cohesion Technologies, Inc.||Crosslinked polymer compositions and methods for their use|
|US6056993||Apr 17, 1998||May 2, 2000||Schneider (Usa) Inc.||Porous protheses and methods for making the same wherein the protheses are formed by spraying water soluble and water insoluble fibers onto a rotating mandrel|
|US6060451||Mar 20, 1995||May 9, 2000||The National Research Council Of Canada||Thrombin inhibitors based on the amino acid sequence of hirudin|
|US6066156||Mar 11, 1999||May 23, 2000||Advanced Cardiovascular Systems, Inc.||Temperature activated adhesive for releasably attaching stents to balloons|
|US6071266||Oct 23, 1998||Jun 6, 2000||Kelley; Donald W.||Lubricious medical devices|
|US6074659||Jul 10, 1998||Jun 13, 2000||Noerx Corporation||Therapeutic inhibitor of vascular smooth muscle cells|
|US6080177||Apr 28, 1998||Jun 27, 2000||Igaki; Keiji||Luminal stent, holding structure therefor and device for attaching luminal stent|
|US6080488||Mar 24, 1998||Jun 27, 2000||Schneider (Usa) Inc.||Process for preparation of slippery, tenaciously adhering, hydrophilic polyurethane hydrogel coating, coated polymer and metal substrate materials, and coated medical devices|
|US6083258||May 28, 1998||Jul 4, 2000||Yadav; Jay S.||Locking stent|
|US6093463||Mar 20, 1998||Jul 25, 2000||Intella Interventional Systems, Inc.||Medical devices made from improved polymer blends|
|US6096070||May 16, 1996||Aug 1, 2000||Med Institute Inc.||Coated implantable medical device|
|US6096525||Nov 26, 1997||Aug 1, 2000||Meadox Medicals, Inc.||Bonding bio-active materials to expanded polytetrafluoroethylene or polyethylene terephthalate via an isocyanate-terminated spacer|
|US6099562||Dec 22, 1997||Aug 8, 2000||Schneider (Usa) Inc.||Drug coating with topcoat|
|US6103230||Oct 2, 1998||Aug 15, 2000||University Of Pittsburgh Of The Commonwealth System Of Higher Education||Methods for promoting wound healing and treating transplant-associated vasculopathy|
|US6107416||Feb 1, 1999||Aug 22, 2000||Scimed Life Systems, Inc.||Polymer coatings grafted with polyethylene oxide chains containing covalently bonded bio-active agents|
|US6110188||Mar 9, 1998||Aug 29, 2000||Corvascular, Inc.||Anastomosis method|
|US6113629||May 1, 1998||Sep 5, 2000||Micrus Corporation||Hydrogel for the therapeutic treatment of aneurysms|
|US6117979||Aug 18, 1997||Sep 12, 2000||Medtronic, Inc.||Process for making a bioprosthetic device and implants produced therefrom|
|US6120536||Jun 13, 1996||Sep 19, 2000||Schneider (Usa) Inc.||Medical devices with long term non-thrombogenic coatings|
|US6120904||May 24, 1999||Sep 19, 2000||Schneider (Usa) Inc.||Medical device coated with interpenetrating network of hydrogel polymers|
|US6121027||Aug 15, 1997||Sep 19, 2000||Surmodics, Inc.||Polybifunctional reagent having a polymeric backbone and photoreactive moieties and bioactive groups|
|US6125523||Nov 20, 1998||Oct 3, 2000||Advanced Cardiovascular Systems, Inc.||Stent crimping tool and method of use|
|US6127173||Sep 22, 1998||Oct 3, 2000||Ribozyme Pharmaceuticals, Inc.||Nucleic acid catalysts with endonuclease activity|
|US6129761||Jun 7, 1995||Oct 10, 2000||Reprogenesis, Inc.||Injectable hydrogel compositions|
|US6129928||Sep 4, 1998||Oct 10, 2000||Icet, Inc.||Biomimetic calcium phosphate implant coatings and methods for making the same|
|US6150630||Apr 17, 1998||Nov 21, 2000||The Regents Of The University Of California||Laser machining of explosives|
|US6153252||Apr 19, 1999||Nov 28, 2000||Ethicon, Inc.||Process for coating stents|
|US6159951||Dec 2, 1997||Dec 12, 2000||Ribozyme Pharmaceuticals Inc.||2'-O-amino-containing nucleoside analogs and polynucleotides|
|US6160084||Feb 23, 1999||Dec 12, 2000||Massachusetts Institute Of Technology||Biodegradable shape memory polymers|
|US6165212||Jun 28, 1999||Dec 26, 2000||Corvita Corporation||Expandable supportive endoluminal grafts|
|US6166130||Apr 30, 1999||Dec 26, 2000||Cohesion Technologies, Inc.||Method of using crosslinked polymer compositions in tissue treatment applications|
|US6169170||Sep 3, 1997||Jan 2, 2001||Lynx Therapeutics, Inc.||Oligonucleotide N3′→N5′Phosphoramidate Duplexes|
|US6171609||Oct 23, 1995||Jan 9, 2001||Neorx Corporation||Therapeutic inhibitor of vascular smooth muscle cells|
|US6174330||Aug 1, 1997||Jan 16, 2001||Schneider (Usa) Inc||Bioabsorbable marker having radiopaque constituents|
|US6177523||Jul 14, 1999||Jan 23, 2001||Cardiotech International, Inc.||Functionalized polyurethanes|
|US6183505||Mar 11, 1999||Feb 6, 2001||Medtronic Ave, Inc.||Method of stent retention to a delivery catheter balloon-braided retainers|
|US6187045||Feb 10, 1999||Feb 13, 2001||Thomas K. Fehring||Enhanced biocompatible implants and alloys|
|US6210715||Mar 31, 1998||Apr 3, 2001||Cap Biotechnology, Inc.||Calcium phosphate microcarriers and microspheres|
|US6224626||Apr 1, 1999||May 1, 2001||Md3, Inc.||Ultra-thin expandable stent|
|US6228845||Oct 21, 1998||May 8, 2001||Medtronic, Inc.||Therapeutic intraluminal stents|
|US6240616||Apr 15, 1997||Jun 5, 2001||Advanced Cardiovascular Systems, Inc.||Method of manufacturing a medicated porous metal prosthesis|
|US6245076||May 22, 2000||Jun 12, 2001||Advanced Cardiovascular Systems, Inc.||Temperature activated adhesive for releasably attaching stents to balloons|
|US6245103||Aug 1, 1997||Jun 12, 2001||Schneider (Usa) Inc||Bioabsorbable self-expanding stent|
|US6248344||Apr 15, 1998||Jun 19, 2001||Heimo Ylänen||Composite and its use|
|US6251135||Mar 8, 1999||Jun 26, 2001||Schneider (Usa) Inc||Radiopaque marker system and method of use|
|US6251142||Dec 9, 1997||Jun 26, 2001||Sorin Biomedica Cardio S.P.A.||Implantation device and a kit including the device|
|US6273913||Apr 16, 1998||Aug 14, 2001||Cordis Corporation||Modified stent useful for delivery of drugs along stent strut|
|US6281262||Nov 12, 1998||Aug 28, 2001||Takiron Co., Ltd.||Shape-memory, biodegradable and absorbable material|
|US6284333||Feb 25, 1999||Sep 4, 2001||Scimed Life Systems, Inc.||Medical devices made from polymer blends containing low melting temperature liquid crystal polymers|
|US6287332||Jun 25, 1999||Sep 11, 2001||Biotronik Mess- Und Therapiegeraete Gmbh & Co. Ingenieurbuero Berlin||Implantable, bioresorbable vessel wall support, in particular coronary stent|
|US6290721||Oct 21, 1997||Sep 18, 2001||Boston Scientific Corporation||Tubular medical endoprostheses|
|US6293966||Apr 20, 1998||Sep 25, 2001||Cook Incorporated||Surgical stent featuring radiopaque markers|
|US6303901||Apr 21, 2000||Oct 16, 2001||The Regents Of The University Of California||Method to reduce damage to backing plate|
|US6312459||Jun 30, 1999||Nov 6, 2001||Advanced Cardiovascular Systems, Inc.||Stent design for use in small vessels|
|US6327772||Apr 13, 1999||Dec 11, 2001||Medtronic, Inc.||Method for fabricating a planar eversible lattice which forms a stent when everted|
|US6375826||Feb 14, 2000||Apr 23, 2002||Advanced Cardiovascular Systems, Inc.||Electro-polishing fixture and electrolyte solution for polishing stents and method|
|US6379381||Sep 3, 1999||Apr 30, 2002||Advanced Cardiovascular Systems, Inc.||Porous prosthesis and a method of depositing substances into the pores|
|US6387121||Aug 8, 2000||May 14, 2002||Inflow Dynamics Inc.||Vascular and endoluminal stents with improved coatings|
|US6388043||Feb 23, 1999||May 14, 2002||Mnemoscience Gmbh||Shape memory polymers|
|US6395326||May 31, 2000||May 28, 2002||Advanced Cardiovascular Systems, Inc.||Apparatus and method for depositing a coating onto a surface of a prosthesis|
|US6409761||Apr 20, 2001||Jun 25, 2002||G. David Jang||Intravascular stent|
|US6423092||Aug 20, 2001||Jul 23, 2002||Ethicon, Inc.||Biodegradable stent|
|US6461632||Apr 18, 2001||Oct 8, 2002||Synthes (U.S.A.)||Hardenable ceramic hydraulic cement|
|US6464720||Mar 30, 2001||Oct 15, 2002||Cook Incorporated||Radially expandable stent|
|US6479565||Aug 16, 1999||Nov 12, 2002||Harold R. Stanley||Bioactive ceramic cement|
|US6485512||Sep 27, 2000||Nov 26, 2002||Advanced Cardiovascular Systems, Inc.||Two-stage light curable stent and delivery system|
|US6492615||Oct 12, 2000||Dec 10, 2002||Scimed Life Systems, Inc.||Laser polishing of medical devices|
|US6494908||Dec 22, 1999||Dec 17, 2002||Ethicon, Inc.||Removable stent for body lumens|
|US6495156||May 11, 2001||Dec 17, 2002||Merck Patent Gmbh||Biocements having improved compressive strength|
|US6500146 *||Aug 25, 2000||Dec 31, 2002||Cordis Corporation||Balloons for medical devices and fabrication thereof|
|US6511748||Jan 6, 1999||Jan 28, 2003||Aderans Research Institute, Inc.||Bioabsorbable fibers and reinforced composites produced therefrom|
|US6517888||Nov 28, 2000||Feb 11, 2003||Scimed Life Systems, Inc.||Method for manufacturing a medical device having a coated portion by laser ablation|
|US6527801||Apr 13, 2000||Mar 4, 2003||Advanced Cardiovascular Systems, Inc.||Biodegradable drug delivery material for stent|
|US6537589||Jul 25, 2000||Mar 25, 2003||Kyung Won Medical Co., Ltd.||Calcium phosphate artificial bone as osteoconductive and biodegradable bone substitute material|
|US6539607||Sep 13, 2000||Apr 1, 2003||University Of North Carolina At Charlotte||Enhanced biocompatible implants and alloys|
|US6540777||Feb 15, 2001||Apr 1, 2003||Scimed Life Systems, Inc.||Locking stent|
|US6554854||Dec 10, 1999||Apr 29, 2003||Scimed Life Systems, Inc.||Process for laser joining dissimilar metals and endoluminal stent with radiopaque marker produced thereby|
|US6565599||Dec 28, 2000||May 20, 2003||Advanced Cardiovascular Systems, Inc.||Hybrid stent|
|US6569191||Jul 27, 2000||May 27, 2003||Bionx Implants, Inc.||Self-expanding stent with enhanced radial expansion and shape memory|
|US6569193||Jul 22, 1999||May 27, 2003||Advanced Cardiovascular Systems, Inc.||Tapered self-expanding stent|
|US6572672||May 17, 2002||Jun 3, 2003||Nanoproducts Corporation||Nanotechnology for biomedical products|
|US6572813||Jan 13, 2000||Jun 3, 2003||Advanced Cardiovascular Systems, Inc.||Balloon forming process|
|US6574851||Jul 31, 2000||Jun 10, 2003||Advanced Cardiovascular Systems, Inc.||Stent made by rotational molding or centrifugal casting and method for making the same|
|US6585755||Jun 29, 2001||Jul 1, 2003||Advanced Cardiovascular||Polymeric stent suitable for imaging by MRI and fluoroscopy|
|US6592614||Dec 1, 2000||Jul 15, 2003||Medtronic Ave, Inc.||Cuffed endoluminal prosthesis|
|US6592617||Jan 16, 2001||Jul 15, 2003||Boston Scientific Scimed, Inc.||Three-dimensional braided covered stent|
|US6613072||Jul 18, 1997||Sep 2, 2003||Gore Enterprise Holdings, Inc.||Procedures for introducing stents and stent-grafts|
|US6626939||Dec 18, 1997||Sep 30, 2003||Boston Scientific Scimed, Inc.||Stent-graft with bioabsorbable structural support|
|US6635269||Nov 24, 1998||Oct 21, 2003||Morphoplant Gmbh||Immobilizing mediator molecules via anchor molecules on metallic implant materials containing oxide layer|
|US6645243||Jan 8, 1998||Nov 11, 2003||Sorin Biomedica Cardio S.P.A.||Stent for angioplasty and a production process therefor|
|US6645422||Jul 27, 2001||Nov 11, 2003||Jomed, Inc.||Method for manufacturing a balloon for a dilation catheter|
|US6656162||Dec 9, 2002||Dec 2, 2003||Microchips, Inc.||Implantable drug delivery stents|
|US6664335||Nov 30, 2000||Dec 16, 2003||Cardiac Pacemakers, Inc.||Polyurethane elastomer article with “shape memory” and medical devices therefrom|
|US6666214||Sep 28, 2001||Dec 23, 2003||Psimedica Limited||Biomaterial|
|US6667049||Mar 28, 2001||Dec 23, 2003||Ethicon, Inc.||Relic process for producing bioresorbable ceramic tissue scaffolds|
|US6669723||Nov 22, 2002||Dec 30, 2003||Scimed Life Systems, Inc.||Stent having variable properties and method of its use|
|US6676697||Mar 17, 1998||Jan 13, 2004||Medinol Ltd.||Stent with variable features to optimize support and method of making such stent|
|US6679980||Jun 13, 2001||Jan 20, 2004||Advanced Cardiovascular Systems, Inc.||Apparatus for electropolishing a stent|
|US6689375||Oct 14, 2002||Feb 10, 2004||Coripharm Medizinprodukte Gmbh & Co. Kg||Resorbable bone implant material and method for producing the same|
|US6695920||Jun 27, 2001||Feb 24, 2004||Advanced Cardiovascular Systems, Inc.||Mandrel for supporting a stent and a method of using the mandrel to coat a stent|
|US6706273||Aug 14, 2000||Mar 16, 2004||Ivoclar Vivadent Ag||Composition for implantation into the human and animal body|
|US6709379||Nov 2, 1999||Mar 23, 2004||Alcove Surfaces Gmbh||Implant with cavities containing therapeutic agents|
|US6719934||Apr 25, 2001||Apr 13, 2004||Boston Scientific Scimed, Inc.||Process for making bioabsorbable self-expanding stent|
|US6719989||Sep 8, 2000||Apr 13, 2004||Pentax Corporation||Sustained release drug carrier, and method of manufacturing sustained release drug carrier|
|US6720402||May 8, 2002||Apr 13, 2004||Mnemoscience Gmbh||Shape memory polymers|
|US6746773||Sep 25, 2001||Jun 8, 2004||Ethicon, Inc.||Coatings for medical devices|
|US6752826||Dec 14, 2001||Jun 22, 2004||Thoratec Corporation||Layered stent-graft and methods of making the same|
|US6753007||Nov 1, 2001||Jun 22, 2004||Wright Medical Technology, Inc.||Controlled release composite|
|US6764505||Apr 12, 2001||Jul 20, 2004||Advanced Cardiovascular Systems, Inc.||Variable surface area stent|
|US6818063||Sep 24, 2002||Nov 16, 2004||Advanced Cardiovascular Systems, Inc.||Stent mandrel fixture and method for minimizing coating defects|
|US6846323||May 15, 2003||Jan 25, 2005||Advanced Cardiovascular Systems, Inc.||Intravascular stent|
|US6915560 *||May 23, 2003||Jul 12, 2005||Boston Scientific Scimed, Inc.||Apparatus for contracting, loading or crimping self-expanding and balloon expandable stent devices|
|US7066952||Oct 30, 2002||Jun 27, 2006||Kabushikikaisha Igaki Iryo Sekkei||Method for manufacturing yarn for vessel stent|
|US7070615||Mar 13, 2001||Jul 4, 2006||Keiji Igaki||Linear material for blood vessel stent and blood vessel stent utilizing same|
|US7083639||Sep 26, 2001||Aug 1, 2006||Medtronic Vascular, Inc.||Stent delivery catheter with grooved balloon and methods of making same|
|US7128868 *||Jan 10, 2003||Oct 31, 2006||Boston Scientific Scimed, Inc.||Balloon wing forming apparatus and method|
|US20010014821||Nov 16, 1998||Aug 16, 2001||Mohamad Ike Juman||Balloon catheter and stent delivery system having enhanced stent retention|
|US20010044652||Jun 14, 2001||Nov 22, 2001||Moore Brian Edward||Stents with multi-layered struts|
|US20020002399||May 8, 2001||Jan 3, 2002||Huxel Shawn Thayer||Removable stent for body lumens|
|US20020004060||Jul 17, 1998||Jan 10, 2002||Bernd Heublein||Metallic implant which is degradable in vivo|
|US20020004101||Aug 30, 2001||Jan 10, 2002||Schneider (Usa) Inc.||Drug coating with topcoat|
|US20020062148||Feb 26, 1997||May 23, 2002||Charles C. Hart||Kinetic stent|
|US20020065553||Dec 3, 2001||May 30, 2002||Scimed Life System, Inc.||Method for manufacturing a medical device having a coated portion by laser ablation|
|US20020077592||Oct 22, 2001||Jun 20, 2002||Boston Scientific Corporation||Replenishable stent and delivery system|
|US20020111590||Sep 25, 2001||Aug 15, 2002||Davila Luis A.||Medical devices, drug coatings and methods for maintaining the drug coatings thereon|
|US20020116050||Feb 26, 2002||Aug 22, 2002||Scimed Life Systems, Inc.||Stents with temporary retaining bands|
|US20020125617||Mar 6, 2001||Sep 12, 2002||Advanced Cardiovascular Systems, Inc.||Adjustable length mold assemblies|
|US20020138133 *||May 20, 2002||Sep 26, 2002||Scimed Life Systems, Inc.||Stent with variable properties|
|US20020151965||Jun 18, 2002||Oct 17, 2002||Micro Therapeutics, Inc.||Rolled stent with waveform perforation pattern|
|US20020161114||Jan 22, 2002||Oct 31, 2002||Gunatillake Pathiraja A.||Shape memory polyurethane or polyurethane-urea polymers|
|US20030028241||Aug 2, 2001||Feb 6, 2003||Stinson Jonathan Swift||Method for enhancing sheet or tubing metal stent radiopacity|
|US20030028246||Apr 29, 2002||Feb 6, 2003||Palmaz Julio C.||Compliant implantable medical devices and methods of making same|
|US20030033001||Apr 27, 2001||Feb 13, 2003||Keiji Igaki||Stent holding member and stent feeding system|
|US20030055488||Oct 30, 2002||Mar 20, 2003||Keiji Igaki||Method for manufacturing yarn for vessel stent|
|US20030083732||Oct 25, 2001||May 1, 2003||Stinson Jonathan S.||Balloon expandable polymer stent with reduced elastic recoil|
|US20030093107||Sep 27, 2002||May 15, 2003||Edward Parsonage||Medical devices comprising nanocomposites|
|US20030100865||Dec 9, 2002||May 29, 2003||Santini John T.||Implantable drug delivery stents|
|US20030105518||Jan 10, 2003||Jun 5, 2003||Debashis Dutta||Biodegradable drug delivery material for stent|
|US20030105530||Dec 4, 2001||Jun 5, 2003||Inion Ltd.||Biodegradable implant and method for manufacturing one|
|US20030171053||Dec 10, 2002||Sep 11, 2003||University Of Washington||Medical devices comprising small fiber biomaterials, and methods of use|
|US20030187158||Apr 8, 2003||Oct 2, 2003||The Procter & Gamble Company||High molecular weight polyolefin and catalyst and process for polymerising said polyolefin|
|US20030187495||Apr 1, 2002||Oct 2, 2003||Cully Edward H.||Endoluminal devices, embolic filters, methods of manufacture and use|
|US20030208254||May 3, 2002||Nov 6, 2003||James Shortt||Method and apparatus for mounting a stent onto a stent delivery system|
|US20030208259||Jun 26, 2001||Nov 6, 2003||Pentech Medical Devices Ltd.||Polymeric stents and other surgical articles|
|US20030209835||Mar 28, 2003||Nov 13, 2003||Iksoo Chun||Method of forming a tubular membrane on a structural frame|
|US20030226833||May 12, 2003||Dec 11, 2003||Scimed Life Systems, Inc.||Laser cutting of stents and other medical devices|
|US20030236563||Jun 20, 2002||Dec 25, 2003||Dan Fifer||Stent delivery catheter with retention bands|
|US20040000361||Jun 27, 2002||Jan 1, 2004||Thomas Trozera||Method of manufacturing an implantable stent having improved mechanical properties|
|US20040093077||Aug 6, 2003||May 13, 2004||Jason White||Stent with micro-latching hinge joints|
|US20040098090||Jan 15, 2003||May 20, 2004||Williams Michael S.||Polymeric endoprosthesis and method of manufacture|
|US20040098095||Sep 30, 2003||May 20, 2004||Burnside Diane K.||Stent-graft with bioabsorbable structural support|
|US20040111149||Aug 6, 2003||Jun 10, 2004||Stinson Jonathan S.||Bioabsorbable marker having radiopaque constituents|
|US20040127970||Dec 30, 2002||Jul 1, 2004||Saunders Richard J.||Polymer link hybrid stent|
|US20040143317||Jan 17, 2003||Jul 22, 2004||Stinson Jonathan S.||Medical devices|
|US20040167610||Feb 26, 2003||Aug 26, 2004||Fleming James A.||Locking stent|
|US20050004663||Jun 21, 2004||Jan 6, 2005||Llanos Gerard H.||Heparin barrier coating for controlled drug release|
|US20050137678||Dec 22, 2003||Jun 23, 2005||Medtronic Vascular, Inc.||Low profile resorbable stent|
|US20050177130||Feb 10, 2004||Aug 11, 2005||Angioscore, Inc.||Balloon catheter with spiral folds|
|US20050187615||Feb 18, 2005||Aug 25, 2005||Williams Michael S.||Polymeric endoprostheses with enhanced strength and flexibility and methods of manufacture|
|US20050196485||Jan 13, 2005||Sep 8, 2005||Martin Cass||Heat transfer system for a mold|
|US20060020330||Jul 26, 2004||Jan 26, 2006||Bin Huang||Method of fabricating an implantable medical device with biaxially oriented polymers|
|US20060076708||Jul 18, 2005||Apr 13, 2006||Bin Huang||Method of fabricating a biaxially oriented implantable medical device|
|US20060211952||Mar 15, 2006||Sep 21, 2006||Wilson-Cook Medical Inc.||Wire guides having novel outer surface areas and reservoirs for enhancing hydrophilic properties and delivering therapeutic agents|
|US20060224226||Mar 31, 2005||Oct 5, 2006||Bin Huang||In-vivo radial orientation of a polymeric implantable medical device|
|US20070253996||Apr 28, 2006||Nov 1, 2007||Huang Bin||Method of fabricating an implantable medical device by controlling crystalline structure|
|US20070253999||May 31, 2006||Nov 1, 2007||Bin Huang||Method of fabricating an implantable medical device to reduce chance of late inflammatory response|
|US20070282433||Jun 1, 2006||Dec 6, 2007||Limon Timothy A||Stent with retention protrusions formed during crimping|
|US20070290412||Jun 19, 2006||Dec 20, 2007||John Capek||Fabricating a stent with selected properties in the radial and axial directions|
|US20070293938||Jun 15, 2006||Dec 20, 2007||Gale David C||Methods of fabricating stents with enhanced fracture toughness|
|US20080001333||Jun 30, 2006||Jan 3, 2008||Klaus Kleine||Method of fabricating a stent with features by blow molding|
|US20090001633||Jun 29, 2007||Jan 1, 2009||Limon Timothy A||Method Of Manufacturing A Stent From A Polymer Tube|
|US20090005860||Jun 27, 2007||Jan 1, 2009||Gale David C||Method to fabricate a stent having selected morphology to reduce restenosis|
|US20090012598||Jul 8, 2008||Jan 8, 2009||Abbate Anthony J||Method of fabricating an implantable medical device by deformation of a tube or a sheet|
|US20090146348||Dec 11, 2007||Jun 11, 2009||Bin Huang||Method of fabrication a stent from blow molded tubing|
|DE4407079B4||Mar 3, 1994||Jan 18, 2007||Boston Scientific Ltd., St. Michael||Intraluminal-Aufspannvorrichtung und Transplantat|
|DE19731021A1||Jul 18, 1997||Jan 21, 1999||Meyer Joerg||In vivo abbaubares metallisches Implantat|
|DE19856983A1||Dec 10, 1998||Dec 30, 1999||Biotronik Mess & Therapieg||Implantierbare, bioresorbierbare Gefäßwandstütze, insbesondere Koronarstent|
|EP0108171B1||Oct 22, 1982||May 4, 1988||Meadox Medicals, Inc.||Synthetic woven double-velour graft|
|EP0144534A2||Aug 16, 1984||Jun 19, 1985||Allied Corporation||prosthetic devices|
|EP0364787B1||Sep 29, 1989||Mar 4, 1992||EXPANDABLE GRAFTS PARTNERSHIP a Texas General Partnership||Expandable intraluminal graft|
|EP0397500B1||May 10, 1990||Aug 2, 1995||United States Surgical Corporation||Synthetic semiabsorbable yarn, fabric and tubular prosthesis|
|EP0464755B1||Jul 1, 1991||May 3, 1995||Nissho Corporation||Artificial tubular organ|
|EP0493788B1||Dec 23, 1991||Sep 25, 1996||MUDR. MILAN KRAJICEK CSc.||Three-layer vascular prosthesis|
|EP0554082B1||Jan 28, 1993||Dec 29, 1997||Advanced Cardiovascular Systems, Inc.||Expandable stent|
|EP0578998B1||Jun 22, 1993||Oct 8, 1997||Strecker, Ernst Peter, Dr.-med.Prof.||Implantable percutaneous endoprosthesis|
|EP0583170B1||Aug 12, 1993||Jul 16, 1997||Adcock Ingram Limited||Hydrogel compositions and methods for the preparation thereof|
|EP0604022A1||Nov 24, 1993||Jun 29, 1994||Advanced Cardiovascular Systems, Inc.||Multilayered biodegradable stent and method for its manufacture|
|EP0621017A1||Apr 25, 1994||Oct 26, 1994||Advanced Cardiovascular Systems, Inc.||Ratcheting stent|
|EP0623354B1||Apr 20, 1994||Oct 2, 2002||Medtronic, Inc.||Intravascular stents|
|EP0665023B1||Jul 13, 1994||Apr 21, 2004||Otsuka Pharmaceutical Co., Ltd.||Medical material and process for producing the same|
|EP0709068A2||Oct 27, 1995||May 1, 1996||Medinol Ltd.||X-ray visible stent|
|EP0970711B1||Jun 29, 1999||Oct 13, 2004||Ethicon, Inc.||Process for coating stents|
|EP1800628A2||Dec 9, 2006||Jun 27, 2007||Cordis Corporation||Polymeric stent having modified molecular structures in selected regions of the flexible connectors|
|GB2102827B||Title not available|
|GB2247696B||Title not available|
|1||Anonymous, Bioabsorbable stent mounted on a catheter having optical coherence tomography capabilities, Research Disclosure, Sep. 2004, pp. 1159-1162.|
|2||Ansari, End-to-end tubal anastomosis using an absorbable stent, Fertility and Sterility, vol. 32(2), pp. 197-201 (Aug. 1979).|
|3||Ansari, Tubal Reanastomosis Using Absorbable Stent, International Journal of Fertility, vol. 23, No. 4, pp. 242-243 (1978).|
|4||Answers.com blow molding; retrieved from www.answers.com/blow%20molding#Stretch- blow-molding, Jun. 26, 2009, 11 pgs.|
|5||Answers.com blow molding; retrieved from www.answers.com/blow%20molding#Stretch— blow—molding, Jun. 26, 2009, 11 pgs.|
|6||Bull, Parylene Coating for Medical Applications, Medical Product Manufacturing News 1 pg. (Mar. 1993).|
|7||Casper et al., Fiber-Reinforced Absorbable Composite for Orthopedic Surgery, Polymeric Materials Science and Engineering, 53: pp. 497-501 (1985).|
|8||Detweiler et al., Gastrointestinal Sutureless Anastomosis Using Fibrin Glue: Reinforcement of the Sliding Absorbable Intraluminal Nontoxic Stent and Development of a Stent Placement Device, Journal of Investigative Surgery, vol. 9(2), pp. 111-130 (Mar./Apr. 1996).|
|9||Detweiler et al., Sliding, Absorbable, Reinforced Ring and an Axially Driven Stent Placement Device for Sutureless Fibrin Glue Gastrointestinal Anastomisis, Journal of Investigative Surgery, vol. 9(6), pp. 495-504 (Nov./Dec. 1996).|
|10||Detweiler et al., Sutureless Anastomosis of the Small Intestine and the Colon in Pigs Using an Absorbable Intraluminal Stent and Fibrin Glue, Journal of Investigative Surgery, vol. 8(2), pp. 129-140 (Mar. 1995).|
|11||Detweiler et al., Sutureless Cholecystojejunostomy in Pigs Using an Absorbable Intraluminal Stent and Fibrin Glue, Journal of Investigative Surgery, vol. 9(1), pp. 13-26 (Jan./Feb. 1996).|
|12||Devanathan et al., Polymeric Conformal Coatings for Implantable Electronic Devices, IEEE Transactions on Biomedical Engineering, vol. BME-27(11), pp. 671-675 (1980).|
|13||Elbert et al., Conjugate Addition Reactions Combined with Free-Radical Cross-Linking for the Design of Materials for Tissue Engineering, Biomacromolecules 2, pp. 430-441 (2001).|
|14||Feng-Chun et al., Assessment of Tissue Blood Flow Following Small Artery Welding with an Intraluminal Dissolvable Stent, Microsurgery, vol. 19(3), pp. 148-152 (1999).|
|15||Hahn et al., Biocompatibility of Glow-Discharge-Polymerized Films and Vacuum-Deposited Parylene, J Applied Polymer Sci, 38, pp. 55-64 (1984).|
|16||Hahn et al., Glow Discharge Polymers as Coatings for Implanted Devices, ISA, pp. 109-111 (1981).|
|17||Kelley et al., Totally Resorbable High-Strength Composite Material, Advances in Biomedical Polymers, 35, pp. 75-85 (1987).|
|18||Kubies et al., Microdomain Structure in polylactide-block-poly(ethylene oxide) copolymer films, Biomaterials 21, pp. 529-536 (2000).|
|19||Kutryk et al., Coronary Stenting: Current Perspectives, a companion to the Handbook of Coronary Stents 16 pgs. (1999).|
|20||Martin et al., Enhancing the biological activity of immobilized osteopontin using a type-1 collagen affinity coating, J. Biomed. Mater Res 70A, pp. 10-19 (2004).|
|21||Mauduit et al., Hydrolytic degradation of films prepared from blends of high and low molecular weight poly(DL-lactic acid)s, J. Biomed. Mater. Res. v. 30, pp. 201-207 (1996).|
|22||Middleton et al., Synthetic biodegradable polymers as orthopedic devices, Biomaterials, vol. 21, pp. 2335-2346 (2000).|
|23||Muller et al., Advances in Coronary Angioplasty: Endovascular Stents, Coron. Arter. Dis., 1(4), pp. 438-448 (Jul./Aug. 1990).|
|24||Nichols et al., Electrical Insulation of Implantable Devices by Composite Polymer Coatings, ISA Transactions, 26(4), pp. 15-18 (1987).|
|25||Peuster et al., A novel approach to temporary stenting: degradable cardiovascular stents produced from corrodible metal-results 6-18 months after implantation into New Zealand white rabbits, Heart 86, pp. 563-569 (2001).|
|26||Pietrzak et al., Bioabsorbable Fixation Devices: Status for the Craniomaxillofacial Surgeon, J. Craniofaxial Surg. 2, pp. 92-96 (1997).|
|27||Pietrzak et al., Bioresorbable implants-practical considerations, Bone v. 19, No. 1, Supplement Jul. 1996: 109S-119S.|
|28||Pietrzak et al., Bioresorbable implants—practical considerations, Bone v. 19, No. 1, Supplement Jul. 1996: 109S-119S.|
|29||Redman, Clinical Experience with Vasovasostomy Utilizing Absorbable Intravasal Stent, Urology, vol. 20(1), pp. 59-61 (Jul. 1982).|
|30||Rust et al., The Effect of Absorbable Stenting on Postoperative Stenosis of the Surgically Enlarged Maxillary Sinus Ostia in a Rabbit Animal Model, Archives of Otolaryngology, vol. 122(12) pp. 1395-1397 (Dec. 1996).|
|31||Schatz, A View of Vascular Stents, Circulation, 79(2), pp. 445-457 (Feb. 1989).|
|32||Schmidt et al., Long-Term Implants of Parylene-C Coated Microelectrodes, Med & Biol Eng & Comp, 26(1), pp. 96-101 (Jan. 1988).|
|33||Spagnuolo et al., Gas 1 is induced by VE-cadherin and vascular endothelial growth factor and inhibits endothelial cell apoptosis, Blood 103, pp. 3005-3012 (2004).|
|34||Tamai et al., Initial and 6-Month Results of Biodegradable Poly-I-Lactic Acid Coronary Stents in Humans, Circulation , pp. 399-404 (2000).|
|35||Tsui et al., Biodegradable Polymeric Stents, Current Interventional Cardiology Reports 3, pp. 10-17 (2001).|
|36||U.S. Appl. No. 10/317,435, Hossainy et al.|
|37||Völkel et al., Targeting of immunoliposomes to endothelial cells using a single-chain Fv fragment directed against human endoglin (CD105), Biochemica et Biophysica Acta 1663, pp. 158-166 (2004).|
|38||von Recum et al., Degradation of polydispersed poly(L-lactic acid) to modulate lactic acid release, Biomaterials 16, pp. 441-445 (1995).|
|39||www.engineeringtoolbox.com/thermal/conductivity/d-429.html., Jun. 26, 2009, 4 pgs.|
|40||www.engineeringtoolbox.com/thermal/conductivity/d—429.html., Jun. 26, 2009, 4 pgs.|
|41||Yau et al. Modern Size-Exclusion Liquid Chromatography, Wiley-Interscience Publication, (1979).|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US8658082||Aug 28, 2012||Feb 25, 2014||Abbott Cardiovascular Systems Inc.||Method of fabricating stents from blow molded tubing|
|US8852263||Jul 12, 2012||Oct 7, 2014||Abbott Cardiovascular Systems Inc.||Stent with nucleating agent|
|US9119905 *||Aug 15, 2014||Sep 1, 2015||Elixir Medical Corporation||Biodegradable endoprostheses and methods for their fabrication|
|US9198782||Apr 14, 2014||Dec 1, 2015||Abbott Cardiovascular Systems Inc.||Manufacturing process for polymeric stents|
|US9205456||Jul 24, 2012||Dec 8, 2015||Abbott Cardiovascular Systems Inc.||Modifying polymer properties with penetrants in the fabrication of bioresorbable scaffolds|
|US9216238||Apr 14, 2014||Dec 22, 2015||Abbott Cardiovascular Systems Inc.||Implantable medical device having reduced chance of late inflammatory response|
|US20150025619 *||Aug 15, 2014||Jan 22, 2015||Elixir Medical Corporation||Biodegradable endoprostheses and methods for their fabrication|
|WO2014202525A1 *||Jun 16, 2014||Dec 24, 2014||Schott Ag||Device and method for transforming a tube|
|U.S. Classification||264/573, 264/235, 264/249, 604/96.01, 264/570, 264/532|
|International Classification||B29D22/00, A61M29/00, B29C43/10, B29C71/00, B29C65/00|
|Cooperative Classification||B29B13/024, B29C33/505, B29C35/041, B29L2023/007, B29C49/04, A61F2/91, B29C53/086, A61F2210/0004, B29C55/24, A61F2240/001, B29C35/045, A61M25/1029|
|European Classification||B29B13/02D2, B29C55/24, B29C53/08C, B29C33/50B|
|Sep 30, 2004||AS||Assignment|
Owner name: ADVANCED CARDIOVASCULAR SYSTEMS, INC., CALIFORNIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:DURCAN, JONATHAN P.;REEL/FRAME:015867/0825
Effective date: 20040927
|Oct 27, 2015||FPAY||Fee payment|
Year of fee payment: 4